FAM83D promotes epithelial-mesenchymal transition, invasion and cisplatin resistance through regulating the AKT/mTOR pathway in non-small-cell lung cancer
| العنوان: | FAM83D promotes epithelial-mesenchymal transition, invasion and cisplatin resistance through regulating the AKT/mTOR pathway in non-small-cell lung cancer |
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| المؤلفون: | Xiaoyan Lin, Antoine M. Snijders, Xianqiang Liu, Guangwei Wei, Pengju Zhang, Jingchao Liu, Yi Xiao, Chunli Yin, Jian-Hua Mao, Yige Wang |
| المصدر: | Cellular Oncology. 43:395-407 |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Epithelial-Mesenchymal Transition, Lung Neoplasms, Mice, Nude, Cell Cycle Proteins, Biology, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, medicine, Animals, Humans, Gene silencing, Neoplasm Invasiveness, Gene Silencing, Epithelial–mesenchymal transition, Lung cancer, Protein kinase B, PI3K/AKT/mTOR pathway, Cell Proliferation, Cisplatin, Mice, Inbred BALB C, TOR Serine-Threonine Kinases, General Medicine, Prognosis, medicine.disease, respiratory tract diseases, 030104 developmental biology, Oncology, Drug Resistance, Neoplasm, Tumor progression, 030220 oncology & carcinogenesis, Cancer research, Molecular Medicine, Microtubule-Associated Proteins, Proto-Oncogene Proteins c-akt, Signal Transduction, medicine.drug |
| الوصف: | FAM83D has been proposed to act as an oncoprotein in several types of human cancer. Its role and mode of action in human non-small cell lung cancer (NSCLC) metastasis and its impact on chemotherapy are as yet, however, poorly understood. FAM83D expression was measured in NSCLC cells and normal lung epithelial cells, as well as in primary NSCLC tissues and corresponding adjacent non-cancerous tissues, using qRT-PCR, Western blotting and immunohistochemistry. FAM83D was stably overexpressed in BEAS2B cells or silenced in A549 and H1299 cells using retroviral or lentiviral vectors. The growth capacity of NSCLC cells was evaluated using MTT and colony formation assays. Epithelial-mesenchymal transition (EMT) was assessed using Western blotting and immunofluorescence. NSCLC cell invasive capacities were assessed using scratch wound healing and Boyden chamber assays. NSCLC cell viability in response to cisplatin treatment was assessed using MTT assays in vitro and a xenograft model in vivo. We found that FAM83D expression levels were significantly elevated in NSCLC cells and tissues, and positively correlated with tumor progression and a poor prognosis. Exogenous FAM83D overexpression promoted, while FAM83D silencing inhibited NSCLC cell proliferation, EMT and invasion. FAM83D silencing also reduced cisplatin resistance. Concordantly, we found that NSCLC patients with a low FAM83D expression benefited most from chemotherapy. Mechanistically, we found that FAM83D activated the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Pharmacological treatment with either AKT or mTOR inhibitors reverted FAM83D-induced tumorigenic phenotypes. Our results suggest a role of FAM83D in NSCLC development. In addition, our results indicate that NSCLC patients exhibiting FAM83D overexpression are likely to benefit from AKT and/or mTOR inhibitor treatment. |
| تدمد: | 2211-3436 2211-3428 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0c8072cac3a3105e616912254037a641 https://doi.org/10.1007/s13402-020-00494-9 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....0c8072cac3a3105e616912254037a641 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 22113436 22113428 |
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