for Journals by Title or ISSN
for Articles by Keywords

Publisher: Biomed Central Ltd.   (Total: 291 journals)

 A  B  C  D  E  F  G  H  I  J  K  L  M  N  O  P  Q  R  S  T  U  V  W  X  Y  Z  

        1 2 | Last   [Sort by number of followers]   [Restore default list]

Showing 1 - 200 of 291 Journals sorted alphabetically
Acta Neuropathologica Communications     Open Access   (Followers: 1, SJR: 2.302, h-index: 14)
Acta Veterinaria Scandinavica     Open Access   (Followers: 3, SJR: 0.425, h-index: 37)
Addiction Science & Clinical Practice     Open Access   (Followers: 7, SJR: 0.956, h-index: 22)
Advances in Simulation     Open Access   (Followers: 2)
Agriculture & Food Security     Open Access   (Followers: 14)
AIDS Research and Therapy     Open Access   (Followers: 14, SJR: 0.839, h-index: 28)
Algorithms for Molecular Biology     Open Access   (Followers: 4, SJR: 0.97, h-index: 24)
Allergy, Asthma and Clinical Immunology     Open Access   (Followers: 25, SJR: 0.782, h-index: 17)
Alzheimer's Research & Therapy     Open Access   (Followers: 6, SJR: 2.046, h-index: 25)
Animal Biotelemetry     Open Access   (Followers: 1)
Annals of Clinical Microbiology and Antimicrobials     Open Access   (Followers: 9, SJR: 0.827, h-index: 36)
Annals of General Psychiatry     Open Access   (Followers: 22, SJR: 0.727, h-index: 32)
Annals of Occupational and Environmental Medicine     Open Access   (Followers: 9)
Annals of Surgical Innovation and Research     Open Access   (Followers: 3, SJR: 0.429, h-index: 10)
Antimicrobial Resistance and Infection Control     Open Access   (Followers: 8, SJR: 1.096, h-index: 12)
Archives of Physiotherapy     Open Access   (Followers: 10)
Archives of Public Health     Open Access   (Followers: 10, SJR: 0.974, h-index: 11)
Arthritis Research & Therapy     Open Access   (Followers: 12, SJR: 1.617, h-index: 111)
Asia Pacific Family Medicine     Open Access   (SJR: 0.227, h-index: 6)
Asthma Research and Practice     Open Access   (Followers: 1)
Basic and Clinical Andrology     Open Access   (SJR: 0.195, h-index: 7)
Behavioral and Brain Functions     Open Access   (Followers: 3, SJR: 0.989, h-index: 42)
Big Data Analytics     Open Access   (Followers: 23)
BioData Mining     Open Access   (Followers: 6, SJR: 1.331, h-index: 13)
Biological Procedures Online     Open Access   (SJR: 0.664, h-index: 31)
Biological Research     Open Access   (SJR: 0.629, h-index: 41)
Biology Direct     Open Access   (Followers: 7, SJR: 3.341, h-index: 45)
Biology of Mood & Anxiety Disorders     Open Access   (Followers: 6, SJR: 0.974, h-index: 4)
Biology of Sex Differences     Open Access   (Followers: 3, SJR: 2.25, h-index: 18)
Biomarker Research     Open Access   (Followers: 2)
Biomaterials Research     Open Access   (Followers: 4)
BioMedical Engineering OnLine     Open Access   (Followers: 7, SJR: 0.531, h-index: 44)
BioPsychoSocial Medicine     Open Access   (Followers: 7, SJR: 0.638, h-index: 20)
Biotechnology for Biofuels     Open Access   (Followers: 10, SJR: 2.557, h-index: 47)
BMC Anesthesiology     Open Access   (Followers: 17, SJR: 0.655, h-index: 23)
BMC Biochemistry     Open Access   (Followers: 14, SJR: 0.792, h-index: 38)
BMC Bioinformatics     Open Access   (Followers: 138, SJR: 1.722, h-index: 144)
BMC Biology     Open Access   (Followers: 68, SJR: 3.871, h-index: 71)
BMC Biophysics     Open Access   (Followers: 5, SJR: 0.309, h-index: 9)
BMC Biotechnology     Open Access   (Followers: 15, SJR: 0.914, h-index: 54)
BMC Cancer     Open Access   (Followers: 26, SJR: 1.627, h-index: 84)
BMC Cardiovascular Disorders     Open Access   (Followers: 21, SJR: 1.023, h-index: 37)
BMC Cell Biology     Open Access   (Followers: 49, SJR: 1.486, h-index: 48)
BMC Clinical Pathology     Open Access   (Followers: 7, SJR: 0.753, h-index: 24)
BMC Complementary and Alternative Medicine     Open Access   (Followers: 13, SJR: 0.783, h-index: 53)
BMC Dermatology     Open Access   (Followers: 13, SJR: 0.854, h-index: 27)
BMC Developmental Biology     Open Access   (Followers: 13, SJR: 1.38, h-index: 55)
BMC Ear, Nose and Throat Disorders     Open Access   (Followers: 1, SJR: 0.636, h-index: 15)
BMC Ecology     Open Access   (Followers: 20, SJR: 1.433, h-index: 27)
BMC Emergency Medicine     Open Access   (Followers: 17, SJR: 0.679, h-index: 22)
BMC Endocrine Disorders     Open Access   (Followers: 6, SJR: 0.733, h-index: 25)
BMC Evolutionary Biology     Open Access   (Followers: 80, SJR: 2.053, h-index: 83)
BMC Family Practice     Open Access   (Followers: 12, SJR: 0.978, h-index: 42)
BMC Gastroenterology     Open Access   (Followers: 15, SJR: 0.999, h-index: 50)
BMC Genetics     Open Access   (Followers: 25, SJR: 1.185, h-index: 51)
BMC Genomics     Open Access   (Followers: 94, SJR: 2.343, h-index: 108)
BMC Geriatrics     Open Access   (Followers: 14, SJR: 1.025, h-index: 41)
BMC Health Services Research     Open Access   (Followers: 15, SJR: 1.128, h-index: 64)
BMC Hematology     Open Access   (Followers: 3)
BMC Immunology     Open Access   (Followers: 10, SJR: 1.087, h-index: 38)
BMC Infectious Diseases     Open Access   (Followers: 16, SJR: 1.51, h-index: 66)
BMC Intl. Health and Human Rights     Open Access   (Followers: 6, SJR: 0.878, h-index: 26)
BMC Medical Education     Open Access   (Followers: 42, SJR: 0.698, h-index: 38)
BMC Medical Ethics     Open Access   (Followers: 18, SJR: 0.859, h-index: 26)
BMC Medical Genetics     Open Access   (Followers: 7, SJR: 1.062, h-index: 52)
BMC Medical Genomics     Open Access   (Followers: 6, SJR: 1.71, h-index: 37)
BMC Medical Imaging     Open Access   (Followers: 8, SJR: 0.651, h-index: 22)
BMC Medical Informatics and Decision Making     Open Access   (Followers: 23, SJR: 1.1, h-index: 44)
BMC Medical Physics     Open Access   (Followers: 5, SJR: 0.564, h-index: 13)
BMC Medical Research Methodology     Open Access   (Followers: 8, SJR: 1.788, h-index: 67)
BMC Medicine     Open Access   (Followers: 13, SJR: 3.415, h-index: 72)
BMC Microbiology     Open Access   (Followers: 12, SJR: 1.391, h-index: 74)
BMC Molecular Biology     Open Access   (Followers: 136, SJR: 1.224, h-index: 53)
BMC Musculoskeletal Disorders     Open Access   (Followers: 18, SJR: 0.881, h-index: 61)
BMC Nephrology     Open Access   (Followers: 9, SJR: 1.113, h-index: 29)
BMC Neurology     Open Access   (Followers: 21, SJR: 1.07, h-index: 45)
BMC Neuroscience     Open Access   (Followers: 16, SJR: 1.318, h-index: 70)
BMC Nursing     Open Access   (Followers: 22, SJR: 0.561, h-index: 20)
BMC Nutrition     Open Access   (Followers: 8)
BMC Obesity     Open Access   (Followers: 5)
BMC Ophthalmology     Open Access   (Followers: 15, SJR: 0.938, h-index: 29)
BMC Oral Health     Open Access   (Followers: 5, SJR: 0.616, h-index: 28)
BMC Palliative Care     Open Access   (Followers: 23, SJR: 1.003, h-index: 25)
BMC Pediatrics     Open Access   (Followers: 14, SJR: 1.097, h-index: 47)
BMC Pharmacology     Open Access   (Followers: 3, SJR: 0.739, h-index: 30)
BMC Pharmacology & Toxicology     Open Access   (Followers: 8, SJR: 0.792, h-index: 10)
BMC Physiology     Open Access   (Followers: 4, SJR: 0.996, h-index: 30)
BMC Plant Biology     Open Access   (Followers: 13, SJR: 1.945, h-index: 71)
BMC Pregnancy and Childbirth     Open Access   (Followers: 20, SJR: 1.397, h-index: 45)
BMC Proceedings     Full-text available via subscription   (Followers: 2, SJR: 0.445, h-index: 9)
BMC Psychiatry     Open Access   (Followers: 27, SJR: 1.307, h-index: 57)
BMC Psychology     Open Access   (Followers: 17)
BMC Public Health     Open Access   (Followers: 152, SJR: 1.372, h-index: 81)
BMC Pulmonary Medicine     Open Access   (Followers: 4, SJR: 1.011, h-index: 38)
BMC Research Notes     Open Access   (Followers: 5, SJR: 0.702, h-index: 38)
BMC Sports Science, Medicine and Rehabilitation     Open Access   (Followers: 26, SJR: 0.471, h-index: 7)
BMC Structural Biology     Open Access   (Followers: 8, SJR: 1.118, h-index: 42)
BMC Surgery     Open Access   (Followers: 9, SJR: 0.675, h-index: 31)
BMC Systems Biology     Open Access   (Followers: 12, SJR: 1.493, h-index: 52)
BMC Urology     Open Access   (Followers: 13, SJR: 0.719, h-index: 27)
BMC Veterinary Research     Open Access   (Followers: 13, SJR: 0.952, h-index: 31)
BMC Women's Health     Open Access   (Followers: 10, SJR: 0.746, h-index: 30)
BMC Zoology     Open Access  
Borderline Personality Disorder and Emotion Dysregulation     Open Access   (Followers: 10)
Breast Cancer Research     Open Access   (Followers: 18, SJR: 3.133, h-index: 107)
Burns & Trauma     Open Access   (Followers: 2)
Burns & Trauma     Open Access   (Followers: 10)
Cancer & Metabolism     Open Access   (Followers: 5)
Cancer Cell Intl.     Open Access   (Followers: 4, SJR: 1.05, h-index: 33)
Cancer Imaging     Open Access   (Followers: 2, SJR: 0.67, h-index: 30)
Cancers of the Head & Neck     Open Access  
Canine Genetics and Epidemiology     Open Access   (Followers: 1)
Cardio-Oncology     Open Access  
Cardiovascular Diabetology     Open Access   (Followers: 9, SJR: 1.757, h-index: 47)
Cardiovascular Ultrasound     Open Access   (Followers: 4, SJR: 0.65, h-index: 31)
Cell Communication and Signaling     Open Access   (Followers: 2, SJR: 1.86, h-index: 37)
Cell Division     Open Access   (Followers: 1, SJR: 2.011, h-index: 32)
Cellular & Molecular Biology Letters     Hybrid Journal   (Followers: 3)
Cerebellum & Ataxias     Open Access   (Followers: 1)
Child and Adolescent Psychiatry and Mental Health     Open Access   (Followers: 22, SJR: 1.25, h-index: 25)
Chinese Medicine     Open Access   (Followers: 2, SJR: 0.655, h-index: 24)
Chinese Neurosurgical J.     Open Access  
Chiropractic & Manual Therapies     Open Access   (Followers: 5, SJR: 0.575, h-index: 19)
Cilia     Open Access   (SJR: 3.69, h-index: 12)
Clinical and Molecular Allergy     Open Access   (Followers: 5, SJR: 0.871, h-index: 24)
Clinical and Translational Allergy     Open Access   (Followers: 2, SJR: 0.119, h-index: 2)
Clinical Diabetes and Endocrinology     Open Access   (Followers: 15)
Clinical Hypertension     Open Access   (Followers: 3)
Clinical Sarcoma Research     Open Access  
Conflict and Health     Open Access   (Followers: 8, SJR: 0.831, h-index: 12)
Contraception and Reproductive Medicine     Open Access  
COPD Research and Practice     Open Access  
Cost Effectiveness and Resource Allocation     Open Access   (Followers: 4, SJR: 0.767, h-index: 26)
Critical Care     Open Access   (Followers: 53, SJR: 2.002, h-index: 112)
Current Opinion in Molecular Therapeutics     Full-text available via subscription   (Followers: 18)
Diabetology & Metabolic Syndrome     Open Access   (Followers: 8, SJR: 0.834, h-index: 23)
Diagnostic Pathology     Open Access   (Followers: 7, SJR: 0.775, h-index: 29)
Disaster and Military Medicine     Open Access   (Followers: 3)
Emerging Themes in Epidemiology     Open Access   (Followers: 13, SJR: 1.172, h-index: 24)
Environmental Health     Open Access   (Followers: 11, SJR: 1.898, h-index: 51)
Epigenetics & Chromatin     Open Access   (Followers: 9, SJR: 4.614, h-index: 26)
European J. of Medical Research     Open Access   (Followers: 1, SJR: 0.592, h-index: 46)
European Review of Aging and Physical Activity     Open Access   (Followers: 8, SJR: 0.597, h-index: 14)
Experimental & Translational Stroke Medicine     Open Access   (Followers: 8, SJR: 0.644, h-index: 13)
Experimental Hematology & Oncology     Open Access   (Followers: 3)
Eye and Vision     Open Access   (Followers: 1)
Fertility Research and Practice     Open Access   (Followers: 1)
Fibrogenesis & Tissue Repair     Open Access   (SJR: 2.496, h-index: 27)
Fisheries and Aquatic Sciences     Open Access   (Followers: 2, SJR: 0.223, h-index: 8)
Flavour     Open Access   (Followers: 3)
Fluids and Barriers of the CNS     Open Access   (Followers: 2, SJR: 2.034, h-index: 29)
Frontiers in Zoology     Open Access   (Followers: 6, SJR: 1.866, h-index: 37)
Genes and Environment     Open Access   (Followers: 1, SJR: 0.161, h-index: 5)
Genetics Selection Evolution     Open Access   (Followers: 7, SJR: 1.341, h-index: 55)
Genome Biology     Open Access   (Followers: 31, SJR: 9.86, h-index: 168)
Genome Medicine     Open Access   (Followers: 7, SJR: 2.915, h-index: 40)
Global Health Research and Policy     Open Access   (Followers: 3)
Globalization and Health     Open Access   (Followers: 5, SJR: 1.261, h-index: 29)
Gut Pathogens     Full-text available via subscription   (Followers: 5, SJR: 1.136, h-index: 18)
Gynecologic Oncology Research and Practice     Open Access   (Followers: 1)
Harm Reduction J.     Open Access   (SJR: 1.239, h-index: 31)
Head & Face Medicine     Open Access   (Followers: 1, SJR: 0.416, h-index: 22)
Health and Quality of Life Outcomes     Open Access   (Followers: 13, SJR: 1.02, h-index: 75)
Health Research Policy and Systems     Open Access   (Followers: 12, SJR: 1.032, h-index: 28)
Hereditary Cancer in Clinical Practice     Open Access   (SJR: 0.678, h-index: 14)
Hereditas     Open Access   (Followers: 2, SJR: 0.423, h-index: 40)
Human Genomics     Open Access   (Followers: 3, SJR: 1.632, h-index: 35)
Human Resources for Health     Open Access   (Followers: 8, SJR: 1.193, h-index: 38)
Immunity & Ageing     Open Access   (Followers: 10, SJR: 1.178, h-index: 28)
Implementation Science     Open Access   (Followers: 15, SJR: 2.259, h-index: 53)
Infectious Agents and Cancer     Open Access   (SJR: 1.085, h-index: 21)
Infectious Diseases of Poverty     Open Access   (Followers: 2, SJR: 0.977, h-index: 12)
Inflammation and Regeneration     Open Access   (Followers: 1)
Intl. Breastfeeding J.     Open Access   (Followers: 23, SJR: 0.934, h-index: 23)
Intl. J. for Equity in Health     Open Access   (Followers: 7, SJR: 1.316, h-index: 31)
Intl. J. of Behavioral Nutrition and Physical Activity     Open Access   (Followers: 24, SJR: 2.216, h-index: 64)
Intl. J. of Health Geographics     Open Access   (Followers: 7, SJR: 1.216, h-index: 48)
Intl. J. of Mental Health Systems     Open Access   (Followers: 7, SJR: 0.484, h-index: 18)
Intl. J. of Pediatric Endocrinology     Open Access   (Followers: 10)
Intl. J. of Retina and Vitreous     Open Access   (Followers: 2)
Investigative Genetics     Open Access   (Followers: 1, SJR: 0.98, h-index: 13)
Irish Veterinary J.     Open Access   (Followers: 7, SJR: 0.477, h-index: 17)
Israel J. of Health Policy Research     Open Access   (SJR: 0.379, h-index: 7)
Italian J. of Pediatrics     Open Access   (Followers: 1, SJR: 0.685, h-index: 20)
J. for ImmunoTherapy of Cancer     Open Access   (Followers: 5)
J. of Angiogenesis Research     Open Access   (Followers: 2)
J. of Animal Science and Biotechnology     Open Access   (Followers: 6, SJR: 0.87, h-index: 10)
J. of Animal Science and Technology     Open Access   (Followers: 2)
J. of Biological Engineering     Open Access   (Followers: 4, SJR: 1.104, h-index: 22)
J. of Biological Research - Thessaloniki     Open Access   (SJR: 0.273, h-index: 10)
J. of Biomedical Semantics     Open Access   (Followers: 2, SJR: 0.903, h-index: 18)
J. of Cardiothoracic Surgery     Open Access   (Followers: 4, SJR: 0.622, h-index: 26)
J. of Cardiovascular Magnetic Resonance     Open Access   (Followers: 1, SJR: 3.238, h-index: 58)
J. of Clinical Movement Disorders     Open Access   (Followers: 3)
J. of Congenital Cardiology     Open Access   (Followers: 3)
J. of Diabetes and Metabolic Disorders     Open Access   (Followers: 9, SJR: 0.693, h-index: 9)
J. of Eating Disorders     Open Access   (Followers: 10, SJR: 1.047, h-index: 7)
J. of Environmental Health Science & Engineering     Open Access   (Followers: 1, SJR: 0.45, h-index: 17)
J. of Ethnobiology and Ethnomedicine     Open Access   (SJR: 1.001, h-index: 40)
J. of Experimental & Clinical Cancer Research     Open Access   (Followers: 2, SJR: 1.702, h-index: 51)

        1 2 | Last   [Sort by number of followers]   [Restore default list]

Journal Cover Journal of Experimental & Clinical Cancer Research
  [SJR: 1.702]   [H-I: 51]   [2 followers]  Follow
  This is an Open Access Journal Open Access journal
   ISSN (Print) 0392-9078 - ISSN (Online) 1756-9966
   Published by Biomed Central Ltd. Homepage  [291 journals]
  • SMURF1 facilitates estrogen receptor ɑ signaling in breast cancer

    • Abstract: Background Estrogen receptor alpha (ER alpha) is expressed in the majority of breast cancers and promotes estrogen-dependent cancer progression. ER alpha positive breast cancer can be well controlled by ER alpha modulators, such as tamoxifen. However, tamoxifen resistance is commonly observed by altered ER alpha signaling. Thus, further understanding of the molecular mechanisms, which regulates ER alpha signaling, is important to improve breast cancer therapy. Methods SMURF1 and ER alpha protein expression levels were measured by western blot, while the ER alpha target genes were measured by real-time PCR. WST-1 assay was used to measure cell viability; the xeno-graft tumor model were used for in vivo study. RNA sequencing was analyzed by Ingenuity Pathway Analysis. Identification of ER alpha signaling was accomplished with luciferase assays, real-time RT-PCR and Western blotting. Protein stability assay and ubiquitin assay was used to detect ER alpha protein degradation. Immuno-precipitation based assays were used to detect the interaction domain between ER alpha and SMURF1. The ubiquitin-based Immuno-precipitation based assays were used to detect the specific ubiquitination manner happened on ER alpha. Results Here, we identify the E3 ligase SMURF1 facilitates ER alpha signaling. We show that depletion SMURF1 decreases ER alpha positive cell proliferation in vitro and in vivo. SMURF1 depletion based RNA-sequence data shows SMURF1 is necessary for ER alpha target gene expression in the transcriptomic scale. Immunoprecipitation indicates that SMURF1 associates with the N-terminal of ER alpha in the cytoplasm via its HECT domain. SMURF1 increases ER alpha stability, possibly by inhibiting K48-specific poly-ubiquitination process on ER alpha protein. Interestingly, SMURF1 expression could be induced via estradiol treatment. Conclusions Our study reveals a novel positive feedback between SMURF1 and ER alpha signaling in supporting breast cancer growth. Targeting SMURF1 could be one promising strategy for ER alpha positive breast cancer treatment.
      PubDate: 2018-02-12
  • 14, 15-EET induces breast cancer cell EMT and cisplatin resistance by
           up-regulating integrin αvβ3 and activating FAK/PI3K/AKT signaling

    • Abstract: Background 14,15-epoxyeicosatrienoic acid (14,15-EET) is an important lipid signaling molecule involved in the regulation of tumor metastasis, however, the role and molecular mechanisms of 14,15-EET activity in breast cancer cell epithelial-mesenchymal transition (EMT) and drug resistance remain enigmatic. Methods The 14, 15-EET level in serum and in tumor or non-cancerous tissue from breast cancer patients was measured by ELISA. qRT-PCR and western blot analyses were used to examine expression of integrin αvβ3. The role of 14, 15-EET in breast cancer cell adhesion, invasion was explored by adhesion and Transwell assays. The role of 14, 15-EET in breast cancer cell cisplatin resistance in vitro was determined by MTT assay. Western blot was conducted to detect the protein expressions of EMT-related markers and FAK/PI3K/AKT signaling. Xenograft models in nude mice were established to explore the roles of 14, 15-EET in breast cancer cells EMT and cisplatin resistance in vivo. Results In the present study, we show that serum level of 14, 15-EET increases in breast cancer patients and 14, 15-EET level of tumor tissue is higher than that of non-cancerous tissue. Moreover, 14, 15-EET increases integrin αvβ3 expression, leading to FAK activation. 14, 15-EET induces breast cancer cell EMT via integrin αvβ3 and FAK/PI3K/AKT cascade activation in vitro. Furthermore, we find that 14, 15-EET induces breast cancer cells EMT and cisplatin resistance in vivo, αvβ3 integrin and the resulting FAK/PI3K/AKT signaling pathway are responsible for 14, 15-EET induced-breast cancer cells cisplatin resistance. Conclusions Our findings suggest that inhibition of 14, 15-EET or inactivation of integrin αvβ3/FAK/PI3K/AKT pathway could serve as a novel approach to reverse EMT and cisplatin resistance in breast cancer cells.
      PubDate: 2018-02-09
  • RHBDD1 promotes colorectal cancer metastasis through the Wnt signaling
           pathway and its downstream target ZEB1

    • Abstract: Background 40–50% of colorectal cancer (CRC) patients develop metastatic disease; the presence of metastasis hinders the effective treatment of cancer through surgery, chemotherapy and radiotherapy, which makes 5-year survival rate extremely low; therefore, studying CRC metastasis is crucial for disease therapy. In the present study, we investigated the role of rhomboid domain containing 1 (RHBDD1) in tumor metastasis of CRC. Methods The expression of RHBDD1 was analyzed in 539 colorectal tumor tissues for its correlation with lymphatic metastasis and distal metastasis. Transwell assay in vitro and pleural metastasis analysis in vivo were performed to determine the functions of RHBDD1 during CRC cells metastasis. RNA-seq analysis, TOP/FOP flash reporter assay, western blot and transwell assay were performed to investigate the underlying mechanism for the function of RHBDD1 on Wnt signaling pathway. Bioinformatics analysis was conducted to investigate epithelial-mesenchymal transition (EMT) and stemness in HCT-116 cells. Tissue microarray analysis, Q-PCR and western blot were performed to determine the correlation of RHBDD1 and Zinc Finger E-Box Binding Homeobox 1 (ZEB1). Results In this study, we found that RHBDD1 expression was positively correlated with lymphatic metastasis and distal metastasis in 539 colorectal tumor tissues. RHBDD1 expression can promote CRC cells metastasis in vitro and in vivo. RNA-Seq analysis showed that the Wnt signaling pathway played a key role in this metastatic regulation. RHBDD1 mainly regulated ser552 and ser675 phosphorylation of β-catenin to activate the Wnt signaling pathway. Rescuing ser552 and ser675 phosphorylation of β-catenin resulted in the recovery of signaling pathway activity, migration, and invasion in CRC cells. RHBDD1 promoted EMT and a stem-like phenotype of CRC cells. RHBDD1 regulated the Wnt/β-catenin target gene ZEB1, a potent EMT activator, at the RNA and protein levels. Clinically, RHBDD1 expression was positively correlated with ZEB1 at the protein level in 71 colon tumor tissues. Conclusions Our findings therefore indicated that RHBDD1 can promote CRC metastasis through the Wnt signaling pathway and ZEB1. RHBDD1 may become a new therapeutic target or clinical biomarker for metastatic CRC.
      PubDate: 2018-02-09
  • Flavagline analog FL3 induces cell cycle arrest in urothelial carcinoma
           cell of the bladder by inhibiting the Akt/PHB interaction to activate the
           GADD45α pathway

    • Abstract: Background Prohibitin 1 (PHB) is a potential target for the treatment of urothelial carcinoma of the bladder (UCB). FL3 is a newly synthesized agent that inhibits cancer cell proliferation by targeting the PHB protein; however, the effect of FL3 in UCB cells remains unexplored. Methods FL3 was identified to be a potent inhibitor of UCB cell viability using CCK-8 (cell counting kit-8) assay. Then a series of in vitro and in vivo experiments were conducted to further demonstrate the inhibitory effect of FL3 on UCB cell proliferation and to determine the underlying mechanisms. Results FL3 inhibited UCB cell proliferation and growth both in vitro and in vivo. By targeting the PHB protein, FL3 inhibited the interaction of Akt and PHB as well as Akt-mediated PHB phosphorylation, which consequently decreases the localization of PHB in the mitochondria. In addition, FL3 treatment resulted in cell cycle arrest in the G2/M phase, and this inhibitory effect of FL3 could be mimicked by knockdown of PHB. Through the microarray analysis of mRNA expression after FL3 treatment and knockdown of PHB, we found that the mRNA expression of the growth arrest and DNA damage-inducible alpha (GADD45α) gene were significantly upregulated. When knocked down the expression of GADD45α, the inhibitory effect of FL3 on cell cycle was rescued, suggesting that FL3-induced cell cycle inhibition is GADD45α dependent. Conclusion Our data provide that FL3 inhibits the interaction of Akt and PHB, which in turn activates the GADD45α-dependent cell cycle inhibition in the G2/M phase.
      PubDate: 2018-02-07
  • Fate of Antibody-Drug Conjugates in Cancer Cells

    • Abstract: Antibody-Drug Conjugates (ADCs) are a class of cancer therapeutics that combines antigen specificity and potent cytotoxicity in a single molecule as they are comprised of an engineered antibody linked chemically to a cytotoxic drug. Four ADCs have received approval by the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) and can be prescribed for metastatic conditions while around 60 ADCs are currently enrolled in clinical trials. The efficacy of an ADC greatly relies on its intracellular trafficking and processing of its components to trigger tumor cell death. A limited number of studies have addressed these critical processes that both challenge and help foster the design of ADCs. This review highlights those mechanisms and their relevance for future development of ADCs as cancer therapeutics.
      PubDate: 2018-02-06
  • miR-302a-5p/367-3p-HMGA2 axis regulates malignant processes during
           endometrial cancer development

    • Abstract: Background Metastasis is one of the main reasons for treatment failure in endometrial cancer. Notably, high mobility group AT-hook 2 (HMGA2) has been recognized as a driving factor of tumour metastasis. microRNAs (miRNAs) are powerful posttranscriptional regulators of HMGA2. Methods The binding sites of miR-302a-5p and miR-367-3p on HMGA2 mRNA were identified using bioinformatics prediction software and were validated via luciferase assay. The expression levels of miR-302a-5p and miR-367-3p were detected using quantitative real-time PCR and in situ hybridization. Western blotting and immunohistochemistry were used to detect the levels of HMGA2 and epithelial-mesenchymal transition pathway-related proteins. Co-immunoprecipitation was used to detect protein interactions. The roles of miR-302a-5p and miR-367-3p in the regulation of HMGA2 during the progression of endometrial cancer were investigated using both in vitro and in vivo assays. Results In the present study, high HMGA2 expression was correlated with poor clinical outcomes in endometrial cancer. The binding sites of miRNAs on HMGA2 mRNA were identified using bioinformatics prediction software and were validated via luciferase assay. In the endometrial cancer cell lines Ishikawa and HEC-1A, the overexpression of miR-302a-5p/367-3p significantly inhibited the expression of HMGA2 mRNA. In endometrial cancer tissues, we showed that miR-302a-5p and miR-367-3p were significantly downregulated and thus inversely correlated with HMGA2. The miR-302a-5p and miR-367-3p expression levels were closely correlated with FIGO stage and lymph node metastasis. High expression of miR-302a-5p/367-3p was correlated with high survival rates in endometrial cancer. In addition, miR-302a-5p/367-3p suppressed the malignant behaviour of endometrial carcinoma cells via the inhibition of HMGA2 expression. Conclusion Our findings indicate that miR-302a-5p/367-3p-mediated expression of HMGA2 regulates the malignant behaviour of endometrial carcinoma cells, which suggests that the miR-302a-5p/367-3p-HMGA2 axis may be a predictive biomarker of endometrial cancer metastasis and patient survival and a potential therapeutic target in metastatic endometrial cancer.
      PubDate: 2018-02-01
  • Integrin-β5, a miR-185-targeted gene, promotes hepatocellular carcinoma
           tumorigenesis by regulating β-catenin stability

    • Abstract: Background The tumour microenvironment is essential for cancer progress and metastasis. Integrin-β5 (ITGB5), a member of the integrin family, has been implicated to mediate the interactions of cells with the extracellular matrix (ECM) and promote tumorigenesis in several malignancies. However, the role of ITGB5 in hepatocellular carcinoma (HCC) is still unknown. Methods The biological function of ITGB5 in HCC was investigated using migration, colony formation assays. The potential molecular mechanism of ITGB5 in regulating HCC tumorigenesis and β-catenin stabilization was investigated by western blotting, co-immunoprecipitation and ubiquitination assays. The expression level of ITGB5 mediated by miR-185 was confirmed by bioinformatic analysis, luciferase assay. The clinical significance of ITGB5 was based on human tissue microarray (TMA) analysis. Results Here, we found that the expression of ITGB5 is increased in HCC tissues. Elevated ITGB5 markedly facilitates HCC cell migration and tumorigenesis in vitro and in vivo. Further mechanistic studies revealed that ITGB5, as a partner of β-catenin, directly interacts with β-catenin and inhibits its degradation, thus leading to WNT/β-catenin activity. Subsequently, we also found that ITGB5 is a direct targeted gene of miR-185. The downregulation of miR-185 in HCC cells promotes an increase in ITGB5. An additional increase of ITGB5 is associated with β-catenin upregulation and a miR-185 decrease in HCC tissues. Conclusions Our data reveal that the miR-185-ITGB5-β-catenin pathway plays an important role in HCC tumorigenesis, and ITGB5 may be a promising specific target for HCC therapy.
      PubDate: 2018-01-31
  • MicroRNA-150 enhances radiosensitivity by inhibiting the AKT pathway in
           NK/T cell lymphoma

    • Abstract: Background Radioresistance is a major challenge during the treatment of NK/T cell lymphoma. This study aimed to investigate the potential role of MicroRNA-150 (miR-150) in increase the sensitivities of NK/T cell lymphoma to ionizing radiation. Results In this study, we found that miR-150 was significantly decreased in NK/T cell lymphoma tissues and cell lines. Low expression of miR-150 was positively associated with therapeutic resistance in 36 NK/T cell lymphoma cases. Our further in vitro and in vivo studies illustrated that overexpression of miR-150 substantially enhanced the sensitivity of NK/T cell lymphoma cells to ionizing radiation treatment. Furthermore, luciferase reporter assays in NK/T cell lymphoma cells transfected with the AKT2 or AKT3 three prime untranslated region reporter constructs established AKT2 and AKT3 as direct targets of miR-150. The phosphatidylinositol 3-kinase inhibitor LY294002 was used to inhibit Akt to verify miR-150 increase NK/T cell lymphoma cell radiorsensitivity through suppress the PI3K/AKT/mTOR pathway. Conclusions Taken together, this study demonstrates that miR-150 might serve as a potential therapeutic sensitizer through inhibition of the AKT pathway in NK/T cell lymphoma treatment.
      PubDate: 2018-01-31
  • The miR-181 family promotes cell cycle by targeting CTDSPL , a
           phosphatase-like tumor suppressor in uveal melanoma

    • Abstract: Background MicroRNAs (miRNAs) have been shown to function in many different cellular processes, including proliferation, apoptosis, differentiation and development. miR-181a, -181b, -181c and -181d are miR-181 members of the family, which has been rarely studied, especially uveal melanoma. Methods The expression level of miR-181 family in human uveal melanoma cell lines was measured via real-time PCR (RT-PCR). The function of miR-181 on cell cycle was detected through Flow Cytometry assay. Microarray assay and Bioinformatics analysis were used to find the potential target of miR-181b, and dual-luciferase reporter assays further identified the target gene. Results MiR-181 family members were found to be highly homologous across different species and their upregulation significantly induces UM cell cycle progression. Of the family members, miR-181b was significantly overexpressed in UM tissues and most UM cells. Bioinformatics and dual luciferase reporter assay confirmed CTDSPL as a target of miR-181b. miR-181b over-expression inhibited CTDSPL expression, which in turn led to the phosphorylation of RB and an accumulation of the downstream cell cycle effector E2F1, promoting cell cycle progression in UM cells. Knockdown CTDSPL using siRNAs showing the same effect, including increase of E2F1 and the progression of cell cycle. Conclusions MiR-181 family members are key negative regulators of CTDSPL-mediated cell cycle progression. These results highlight that miR-181 family members, especially miR-181b, may be useful in the development of miRNA-based therapies and may serve as novel diagnostic and therapeutic candidate for UM.
      PubDate: 2018-01-30
  • Serum DNA integrity index as a potential molecular biomarker in
           endometrial cancer

    • Abstract: Background Circulating cell-free DNA (cfDNA) and its integrity index may represent a rapid and noninvasive “liquid biopsy” biomarker, which gives important complementary information for diagnosis, prognosis, and treatment stratification in cancer patients. The aim of our study was to evaluate the possible role of cfDNA and its integrity index as a complementary tool for endometrial cancer (EC) management. Methods Alu-quantitative real-time PCR (qPCR) analysis wasprformed on 60 serum samples from preoperative EC patients randomly recruited. Both cfDNA content and DNA integrity index were measured by qPCR-Alu115 (representing total cfDNA) and qPCR-Alu247 (corresponding to high molecular weight DNA) and correlated with clinicopathologic characteristics. Lymphovascular space invasion (LVSI) was detected by hematoxylin and eosin staining. In case of doubt, LVSI status was further evaluate by immunohistochemistry using anti-CD31 and anti-CD34 antibodies. Results Total cfDNA content significantly increases in high grade EC. A significant decrease of DNA integrity index was detected in the subset of hypertensive and obese high grade EC. Serum DNA integrity was higher in samples with LVSI. The ordinal regression analysis predicted a significant correlation between decreased integrity index values and hypertension specifically in tumors presenting LVSI. Conclusions Our study supports the utility of serum DNA integrity index as a noninvasive molecular biomarker in EC. We show that a correlation analysis between cfDNA quantitative and qualitative content and clinicopathologic features, such as blood pressure level, body mass index (BMI) and LVSI status, could represent a potential predictive signature to help stratification approaches in EC.
      PubDate: 2018-01-30
  • miR-3928v is induced by HBx via NF-κB/EGR1 and contributes to
           hepatocellular carcinoma malignancy by down-regulating VDAC3

    • Abstract: Background Hepatitis B virus (HBV) plays a critical role in the tumorigenic behavior of human hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) have been reported to participate in HCC development via the regulation of their target genes. However, HBV-modulated miRNAs involved in tumorigenesis remain to be identified. Here, we found that a novel highly expressed miRNA, TLRC-m0008_3p (miR-3928v), may be an important factor that promotes the malignancy of HBV-related HCC. Methods Solexa sequencing was applied to profile miRNAs, and RT-qPCR was used to identify and quantitate miRNAs. We studied miR-3928v function in HCC cell lines by MTT, colony formation, migration/invasion, and vascular mimicry (VM) assays in vitro and by a xenograft tumor model in vivo. Finally, we predicted and verified the target gene of miR-3928v by a reporter assay, studied the function of this target gene, and cloned the promoter of miR-3928v and the transcription factor for use in dual-luciferase reporter assays and EMSAs. Results A variant of miR-3928 (miR-3928v) was identified and found to be highly expressed in HBV (+) HCC tissues. Voltage-dependent anion channel 3 (VDAC3) was validated as a target of miR-3928v and found to mediate the effects of miR-3928v in promoting HCC growth and migration/invasion. Furthermore, HBx protein increased early growth response 1 (EGR1) expression and facilitated its translocation into the nucleus to enhance miR-3928v promoter activity in an NF-κB signaling-dependent manner. Conclusions miR-3928v is induced by HBx through the NF-κB/EGR1 signaling pathway and down-regulates the tumor suppressor gene VDAC3 to accelerate the progression of HCC.
      PubDate: 2018-01-29
  • Over-expression of oncigenic pesudogene DUXAP10 promotes cell
           proliferation and invasion by regulating LATS1 and β-catenin in gastric

    • Abstract: Background Recently, the pesudogenes have emerged as critical regulators in human cancers tumorigenesis and progression, and been identified as a key revelation in post-genomic biology. However, the expression pattern, biological function and mechanisms responsible for these molecules in human gastric cancer (GC) are not fully understood. Methods In this study, we globally assessed the transcriptomic differences of pesudogenes in gastric cancer using publicly available microarray data. DUXAP10 expression levels in GC tissues and cells was detected using quantitative real-time PCR (qPCR). DUXAP10 siRNAs and over-expression vector were transfected into GC cells to down-regulate or up-regulate DUXAP10 expression. Loss- and gain-of function assays were performed to investigate the role of DUXAP10 in GC cells cell proliferation, and invasion. RIP, RNA pulldown, and ChIP assays were used to determine the mechanism of DUXAP10’s regulation of underlying targets. Results The pesudogene DUXAP10 is the only pseudogene that significantly over-expressed in all four GEO datasets, and frequently over-expressed in many other cancers including Liver Hepatocellular carcinoma, Bladder cancer, and Esophageal Cancer. High DUXAP10 expression is associated with GC patients poor prognosis, and knockdown of DUXAP10 significantly inhibits cells proliferation, migration and invasion in GC. Mechanistic investigation shows that DUXAP10 can interact with PRC2 and LSD1 to repress LATS1 expression at transcriptional level, and bind with HuR to maintain the stability of β-catenin mRNA and increase its protein levels at post-transcriptional level. Conclusions Overall, our findings illuminate how increased DUXAP10 confers an oncogenic function in GC development and progression that may serve as a candidate prognostic biomarker and target for clinical management of GC.
      PubDate: 2018-01-27
  • Anti-tumor effects of ONC201 in combination with VEGF-inhibitors
           significantly impacts colorectal cancer growth and survival in vivo
           through complementary non-overlapping mechanisms

    • Abstract: Background Small molecule ONC201 is an investigational anti-tumor agent that upregulates intra-tumoral TRAIL expression and the integrated stress response pathway. A Phase I clinical trial using ONC201 therapy in advanced cancer patients has been completed and the drug has progressed into Phase II trials in several cancer types. Colorectal cancer (CRC) remains one of the leading causes of cancer worldwide and metastatic disease has a poor prognosis. Clinical trials in CRC and other tumor types have demonstrated that therapeutics targeting the vascular endothelial growth factor (VEGF) pathway, such as bevacizumab, are effective in combination with certain chemotherapeutic agents. Methods We investigated the potential combination of VEGF inhibitors such as bevacizumab and its murine-counterpart; along with other anti-angiogenic agents and ONC201 in both CRC xenograft and patient-derived xenograft (PDX) models. We utilized non-invasive imaging and immunohistochemistry to determine potential mechanisms of action. Results Our results demonstrate significant tumor regression or complete tumor ablation in human xenografts with the combination of ONC201 with bevacizumab, and in syngeneic MC38 colorectal cancer xenografts using a murine VEGF-A inhibitor. Imaging demonstrated the impact of this combination on decreasing tumor growth and tumor metastasis. Our results indicate that ONC201 and anti-angiogenic agents act through distinct mechanisms while increasing tumor cell death and inhibiting proliferation. Conclusion With the use of both a murine VEGF inhibitor in syngeneic models, and bevacizumab in human cell line-derived xenografts, we demonstrate that ONC201 in combination with anti-angiogenic therapies such as bevacizumab represents a promising approach for further testing in the clinic for the treatment of CRC.
      PubDate: 2018-01-22
  • MCM6 promotes metastasis of hepatocellular carcinoma via MEK/ERK pathway
           and serves as a novel serum biomarker for early recurrence

    • Abstract: Background The high incidence of recurrence and metastasis of hepatocellular carcinoma (HCC) necessitate the discovery of new predictive biomarkers of invasion and prognosis. Minichromosome maintenance complex component 6 (MCM6), which has been reported to up-regulate in multiple malignancies, was considered to be a novel diagnoses biomarker in HCC. However, its functional contributions and prognostic value remain unclear. Methods The expression of MCM6 was analyzed in 70 HCC tissues and 5 HCC cell lines by immunohistochemistry and real-time RT-PCR. The roles of MCM6 in HCC cell proliferation, migration and invasion were explored by CCK8, Wound healing and Transwell assays, respectively. Western blotting and Immunofluorescence staining were conducted to detect the protein expressions of ERK signaling pathway and EMT-related markers. To verify the above findings in vivo, we established subcutaneous xenograft tumor and orthotopic xenograft tumor models in nude mice. Finally, Enzyme-linked immunosorbent assay was used to evaluate the serum MCM6 level. Results MCM6 was significantly up-regulated in HCC tissues. Increased MCM6 expression was associated with aggressive clinicopathological features and worse prognosis in HCC patients. These results were consistent with our analyses of The Cancer Genome Atlas database (TCGA). Furthermore, knockdown of MCM6 significantly decreased proliferative and migratory/invasive capability of HCC cells in vitro, as well as decreased tumor volume, weight and the number of pulmonary metastases in vivo. Mechanistic analyses indicated that MCM6 promoted EMT and activated MEK/ERK signaling. More importantly, serum MCM6 levels in HCC patients were significantly higher than those in cirrhosis and healthy controls (P < 0.0001), and allowed distinguishing early recurrence with high accuracy (AUC = 0.773). Conclusions Our findings indicate that MCM6 predicts poor prognosis and promotes metastasis in HCC. Postoperative serum MCM6 level could be valuable to detect preclinical early recurrence, indicative of a need for more careful surveillance and aggressive therapeutic intervention.
      PubDate: 2018-01-22
  • A synthetic cell-penetrating peptide derived from nuclear localization
           signal of EPS8 exerts anticancer activity against acute myeloid leukemia

    • Abstract: Background Oncogenic roles of epidermal growth factor receptor pathway substrate no.8 (EPS8) have been widely reported in various tumors, making targeting of EPS8 an appealing prospect. Here, we describe the role of EPS8 in acute myeloid leukemia (AML) and consider the potential of EPS8 as an anti-AML target. Nuclear localization signal (NLS) residues of tumor-associated proteins are crucial for cell cycle progression, and specific inhibitors derived from the NLS have inhibitory effect on cancer cells. The NLS in EPS8 has potential as a specific anti-AML target. Methods Gene Expression Omnibus expression profiles of AML patients were used to test associations between EPS8 expression and AML patient outcome. The biological characteristics of AML cells after EPS8 knockdown were analyzed in vitro and in vivo. A specific peptide (CP-EPS8-NLS) derived from the NLS of EPS8 (amino acids 298–310) was synthesized, and the anti-AML effects of CP-EPS8-NLS were analyzed in cancer cells and in xenograft models. Mutated CP-EPS8-NLS and penetratin served as controls. Results We observed that elevated EPS8 expression in AML patients is associated with poor outcome. Knockdown of EPS8 significantly suppressed the survival of AML cells in vitro and in vivo. CP-EPS8-NLS interfered with EPS8-associated signaling and consequently exerted anti-AML activity. Importantly, CP-EPS8-NLS displayed anti-AML activity in various AML cell types, with diminished activity in PBMCs. CP-ESP8-NLS suppressed U937 cell proliferation, and injection of CP-EPS8-NLS exerted potent antitumor activity in the xenograft tumor models. A synergistic effect of CP-EPS8-NLS and chemotherapeutic agents was also observed in vitro and in vivo. Mechanistically, treatment of various AML cells with CP-EPS8-NLS downregulated the expression of EPS8 and its downstream pathways. Conclusions The function of CP-EPS8-NLS is explained by the presence of a NLS in EPS8, which has been shown to induce nuclear translocation, consequently resulting in EPS8 overexpression. These results indicate that EPS8 is a potential target for AML treatment.
      PubDate: 2018-01-22
  • Autophagy promotes metastasis and glycolysis by upregulating MCT1
           expression and Wnt/β-catenin signaling pathway activation in
           hepatocellular carcinoma cells

    • Abstract: Background Autophagy is a dynamic physiological process that can generate energy and nutrients for cell survival during stress. Autophagy can regulate the migration and invasive ability in cancer cells. However, the connection between autophagy and metabolism is unclear. Monocarboxylate transporter 1 (MCT1) plays an important role in lactic acid transport and H+ clearance in cancer cells, and Wnt/β-catenin signaling can increase cancer cell glycolysis. We investigated whether autophagy promotes glycolysis in hepatocellular carcinoma (HCC) cells by activating the Wnt/β-catenin signaling pathway, accompanied by MCT1 upregulation. Methods Autophagic activity was evaluated using western blotting, immunoblotting, and transmission electron microscopy. The underlying mechanisms of autophagy activation on HCC cell glycolysis were studied via western blotting, and Transwell, lactate, and glucose assays. MCT1 expression was detected using quantitative reverse transcription–PCR (real-time PCR), western blotting, and immunostaining of HCC tissues and the paired adjacent tissues. Results Autophagy promoted HCC cell glycolysis accompanied by MCT1 upregulation. Wnt/β-catenin signaling pathway activation mediated the effect of autophagy on HCC cell glycolysis. β-Catenin downregulation inhibited the autophagy-induced glycolysis in HCC cells, and reduced MCT1 expression in the HCC cells. MCT1 was highly expressed in HCC tissues, and high MCT1 expression correlated positively with the expression of microtubule-associated protein light chain 3 (LC3). Conclusion Activation of autophagy can promote metastasis and glycolysis in HCC cells, and autophagy induces MCT1 expression by activating Wnt/β-catenin signaling. Our study describes the connection between autophagy and glucose metabolism in HCC cells and may provide a potential therapeutic target for HCC treatment.
      PubDate: 2018-01-19
  • INPP4B promotes cell survival via SGK3 activation in NPM1-mutated leukemia

    • Abstract: Background Acute myeloid leukemia (AML) with mutated nucleophosmin (NPM1) has been recognized as a distinct leukemia entity in the 2016 World Health Organization (WHO) classification. The genetic events underlying oncogenesis in NPM1-mutated AML that is characterized by a normal karyotype remain unclear. Inositol polyphosphate 4-phosphatase type II (INPP4B), a new factor in the phosphoinositide-3 kinase (PI3K) pathway-associated cancers, has been recently found a clinically relevant role in AML. However, little is known about the specific mechanistic function of INPP4B in NPM1-mutated AML. Methods The INPP4B expression levels in NPM1-mutated AML primary blasts and AML OCI-AML3 cell lines were determined by qRT-PCR and western blotting. The effect of INPP4B knockdown on OCI-AML3 leukemia cell proliferation was evaluated, using the Cell Counting Kit-8 and colony formation assay. After INPP4B overexpression or knockdown, the activation of serum and glucocorticoid-regulated kinase 3 (SGK3) and AKT was assessed. The effects of PI3K signaling pathway inhibitors on the levels of p-SGK3 in OCI-AML3 cells were tested. The mass of PI (3,4) P2 and PI (3) P was analyzed by ELISA upon INPP4B overexpression. Knockdown of SGK3 by RNA interference and a rescue assay were performed to confirm the critical role of SGK3 in INPP4B-mediated cell survival. In addition, the molecular mechanism underlying INPP4B expression in NPM1-mutated leukemia cells was explored. Finally, Kaplan–Meier survival analysis was conducted on the NPM1-mutated AML cohort stratified into quartiles for INPP4B expression in The Cancer Genome Atlas (TCGA) dataset. Results High expression of INPP4B was observed in NPM1-mutated AML. Knockdown of INPP4B repressed cell proliferation in OCI-AML3 cells, whereas recovered INPP4B rescued this inhibitory effect in vitro. Mechanically, INPP4B enhanced phosphorylated SGK3 (p-SGK3) status, but did not affect AKT activation. SGK3 was required for INPP4B-induced cell proliferation in OCI-AML3 cells. High levels of INPP4B were at least partially caused by the NPM1 mutant via ERK/Ets-1 signaling. Finally, high expression of INPP4B showed a trend towards lower overall survival and event-free survival in NPM1-mutated AML patients. Conclusions Our results indicate that INPP4B promotes leukemia cell survival via SGK3 activation, and INPP4B might be a potential target in the treatment of NPM1-mutated AML.
      PubDate: 2018-01-17
  • Stress-inducible Protein-1 promotes metastasis of gastric cancer via
           Wnt/β-catenin signaling pathway

    • Abstract: Background Stress-Inducible Protein-1 (STIP1) is a co-chaperone that associates directly with heat shock proteins, and regulates motility of various types of cancer. In the present study, we investigated the role of STIP1 on metastasis of gastric cancer (GC). Methods In vivo metastatic experimental model was employed to investigate the effect of STIP1 on metastasis of GC cells. Loss-of-function and gain-of-function experiments were performed to examine the role of STIP1 on metastasis of GC cells. Western blot, immunofluorescence staining, migration and invasion assays, microarray and KEGG pathway analysis were applied to explore the underlying mechanism. Results In current study, we demonstrated that STIP1 promoted lung metastasis of GC cells in vivo. Furthermore, STIP1 significantly enhanced migration and invasion abilities of GC cells. In contrast, knock-down of STIP1 yielded the opposite effects on these phenotypes in vitro. STIP1 promoted tumor metastasis through inducing epithelial-to-mesenchymal transition in GC cells. Mechanistically, STIP1 promoted GC metastasis via up-regulation of targeted genes in Wnt/β-catenin signaling pathway, including c-Myc and Cyclin D1, and accompanied with nuclear translocation of β-catenin. Conclusions Our findings indicate that elevated expression of STIP1 exhibited a metastasis-promoting effect in GC cells through activation of Wnt/β-catenin signaling pathway. STIP1 may be served as a potential therapeutic target for preventing GC metastasis.
      PubDate: 2018-01-15
  • Role of the nervous system in cancer metastasis

    • Abstract: Cancer remains as one of the leading cause of death worldwide. The development of cancer involves an intricate process, wherein many identified and unidentified factors play a role. Although most studies have focused on the genetic abnormalities which initiate and promote cancer, there is overwhelming evidence that tumors interact within their environment by direct cell-to-cell contact and with signaling molecules, suggesting that cancer cells can influence their microenvironment and bidirectionally communicate with other systems. However, only in recent years the role of the nervous system has been recognized as a major contributor to cancer development and metastasis. The nervous system governs functional activities of many organs, and, as tumors are not independent organs within an organism, this system is integrally involved in tumor growth and progression.
      PubDate: 2018-01-15
  • The plant alkaloid tetrandrine inhibits metastasis via autophagy-dependent
           Wnt/β-catenin and metastatic tumor antigen 1 signaling in human liver
           cancer cells

    • Abstract: Background Tetrandrine is a bisbenzylisoquinoline alkaloid isolated from the Chinese medicinal herb Stephania tetrandra S. Moore. We previously demonstrated that tetrandrine exhibits potent antitumor effects in many types of cancer cells. In this study, we investigated the effects of tetrandrine on human hepatocellular carcinoma (HCC) metastasis. Methods The invasion and migration effects were evaluated via wound healing and transwell assays. Immunofluorescence and western blotting analyses were used to investigate the levels of epithelial-mesenchymal transition (EMT)-related protein. A metastasis model was established to investigate the inhibitory effect of tetrandrine on hepatocellular carcinoma metastasis in vivo. Results Tetrandrine inhibits HCC invasion and migration by preventing cell EMT. The underlying mechanism was closely associated with tetrandrine-induced human liver cell autophagy, which inhibits Wnt/β-catenin pathway activity and decreases metastatic tumor antigen 1 (MTA1) expression to modulate cancer cell metastasis. Conclusion Our findings demonstrate, for the first time, that tetrandrine plays a significant role in the inhibition of human hepatocellular carcinoma metastasis and provide novel insights into the application of tetrandrine in clinical HCC treatment.
      PubDate: 2018-01-15
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Tel: +00 44 (0)131 4513762
Fax: +00 44 (0)131 4513327
Home (Search)
Subjects A-Z
Publishers A-Z
Your IP address:
About JournalTOCs
News (blog, publications)
JournalTOCs on Twitter   JournalTOCs on Facebook

JournalTOCs © 2009-