Abstract 4285: Hypoxia-mediated autophagy enhances HGF-induced cancer cell invasion
| العنوان: | Abstract 4285: Hypoxia-mediated autophagy enhances HGF-induced cancer cell invasion |
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| المؤلفون: | Donald P. Bottaro, Young H. Lee |
| المصدر: | Cancer Research. 73:4285-4285 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | MAPK/ERK pathway, Cancer Research, Cell growth, Autophagy, Cell, Biology, Receptor tyrosine kinase, Cell biology, medicine.anatomical_structure, Oncology, Cancer cell, medicine, biology.protein, Hepatocyte growth factor, Signal transduction, medicine.drug |
| الوصف: | The cellular response to hypoxia is a major influence on the aggressiveness of primary tumors, yet much of how this response mechanism influences other signaling pathways is unknown. The MET proto-oncogene, which encodes the tyrosine kinase receptor for hepatocyte growth factor (HGF), is often overexpressed in cancers and can drive cell proliferation, invasion, and metastasis. Prior studies demonstrate that the Met tyrosine-kinase receptor drives cell invasion and metastasis under hypoxic conditions, and this invasive phenotype is lost if MET expression is inhibited. Hypoxia also has been shown to sensitize Met-activated pathways to drive HGF-induced invasion through as yet undefined a molecular mechanism. The high mortality rate of metastatic cancer makes it crucial to understand the functional integration of these two prevalent drivers of metastasis, hypoxia and Met signaling, and to identify ways to selectively block cancer cell invasiveness. We show that a chemically generated pseudo-hypoxic condition enhanced HGF-mediated invasion in the papillary renal cell (PRC) carcinoma cell lines ACHN and UOK112. Under hypoxic conditions, cells generated high levels of ROS, which in turn sensitized the mitogen-activated protein kinase (MAPK) pathway to enhance HGF-driven invasion. Furthermore, hypoxic cells displayed increased autophagy as determined by punctate staining of LC3 II using immunocytochemistry and cleaved LC3 immunoblotting. Inhibition of autophagy decreased cell invasion and hypoxia-mediated autophagy was dependent on MAPK pathway activation. These data suggest that hypoxia promotes the invasiveness of PRC-derived cells by increasing ROS-mediated autophagy to sensitize the MAPK pathway to HGF stimulation. Identifying the specific effectors responsible for the integration these signals will improve our understanding of pro-metastatic invasiveness and potentially identify novels targets for its selective blockade. Citation Format: Young H. Lee, Donald P. Bottaro. Hypoxia-mediated autophagy enhances HGF-induced cancer cell invasion. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4285. doi:10.1158/1538-7445.AM2013-4285 |
| تدمد: | 1538-7445 0008-5472 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::7fe2e0176c278b5b5f92a881295ce873Test https://doi.org/10.1158/1538-7445.am2013-4285Test |
| رقم الانضمام: | edsair.doi...........7fe2e0176c278b5b5f92a881295ce873 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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