Ovarian cancer ascites protects from TRAIL-induced cell death through αvβ5 integrin-mediated focal adhesion kinase and Akt activation
| العنوان: | Ovarian cancer ascites protects from TRAIL-induced cell death through αvβ5 integrin-mediated focal adhesion kinase and Akt activation |
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| المؤلفون: | Denis Lane, Alain Piché, Nadzeya Goncharenko-Khaider, Claudine Rancourt |
| المصدر: | Oncogene. 29:3519-3531 |
| بيانات النشر: | Springer Science and Business Media LLC, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Cancer Research, medicine.medical_specialty, Hot Temperature, Cell Survival, Biology, TNF-Related Apoptosis-Inducing Ligand, Focal adhesion, Growth factor receptor, Cell Line, Tumor, Internal medicine, Genetics, medicine, Humans, Receptors, Vitronectin, Epidermal growth factor receptor, Phosphorylation, Molecular Biology, Protein kinase B, PI3K/AKT/mTOR pathway, Ovarian Neoplasms, Tumor microenvironment, Cell Death, Ascites, medicine.disease, Enzyme Activation, ErbB Receptors, Molecular Weight, Endocrinology, Focal Adhesion Protein-Tyrosine Kinases, Gene Knockdown Techniques, Cancer research, biology.protein, Female, Ovarian cancer, Proto-Oncogene Proteins c-akt |
| الوصف: | Interactions between ovarian cancer cells and the surrounding tumor microenvironment are not well characterized. We have earlier shown that ovarian cancer ascites induces Akt activation and protect tumor cells from TRAIL-induced apoptosis. Here, we investigated the mechanism by which ascites activates Akt. The ability of ovarian cancer ascites to activate Akt and inhibit TRAIL-induced cell death and caspase activity was decreased by heat inactivation, but was retained in ascites fractions5 kDa. The survival promoting activity of ascites was not affected by inhibitors of growth factor receptor including epidermal growth factor receptor (EGFR), VEGFR, FGFR, Her2/neu, and IGF-R1. However, this activity was inhibited by an alphavbeta5 integrin-blocking antibody, but not by blocking antibodies against alphavbeta3, beta1, or beta3 integrins. alphavbeta5 integrin-blocking antibodies also inhibited ascites-induced Akt phosphorylation and c-FLIPs up-regulation. Ovarian cancer ascites induced a rapid phosphorylation of focal adhesion kinase (FAK), which closely correlated with the phosphorylation of Akt overtime. FAK phosphorylation was strongly inhibited by alphavbeta5 integrin-blocking antibodies. Depletion of FAK content by RNA interference was also associated with inhibition of ascites-mediated Akt activation and survival. These results suggest that ovarian cancer ascites induces FAK and Akt activation in an alphavbeta5 integrin-dependent pathway, which confers protection from TRAIL-induced cell death and caspase activation. |
| تدمد: | 1476-5594 0950-9232 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f63aced879ef2a47fb89fae11697ba6dTest https://doi.org/10.1038/onc.2010.107Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f63aced879ef2a47fb89fae11697ba6d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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