Lyn Facilitates Glioblastoma Cell Survival under Conditions of Nutrient Deprivation by Promoting Autophagy
| Autor: | Gaelle Muller-Greven, Jeremy N. Rich, Wei Michael Liu, Amy S. Nowacki, Monica E. Burgett, Candece L. Gladson, Ping Huang, Clark W. Distelhorst, John C. Kappes, Niladri S. Kar, Justin D. Lathia |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Mouse
lcsh:Medicine environment and public health Immunoenzyme Techniques Mice 0302 clinical medicine hemic and lymphatic diseases Molecular Cell Biology Pathology Tumor Cells Cultured lcsh:Science Cellular Stress Responses 0303 health sciences Multidisciplinary Brain Neoplasms hemic and immune systems Animal Models Signaling in Selected Disciplines 3. Good health Cell biology src-Family Kinases Oncology 030220 oncology & carcinogenesis Medicine Stem cell biological phenomena cell phenomena and immunity Tyrosine kinase Research Article Signal Transduction Programmed cell death Clinical Research Design Blotting Western Neurosurgery Biology Signaling Pathways 03 medical and health sciences Model Organisms LYN Diagnostic Medicine Genetics Autophagy Animals Humans Immunoprecipitation Animal Models of Disease 030304 developmental biology Cell Proliferation Oncogenic Signaling Cell growth lcsh:R Lentivirus Cancers and Neoplasms enzymes and coenzymes (carbohydrates) Apoptosis Cell culture Food Cancer research lcsh:Q Surgery Gene Function Molecular Neuroscience Food Deprivation Glioblastoma Biomarkers Neuroscience General Pathology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 8, p e70804 (2013) |
| ISSN: | 1932-6203 |
| Popis: | Members of the Src family kinases (SFK) can modulate diverse cellular processes, including division, death and survival, but their role in autophagy has been minimally explored. Here, we investigated the roles of Lyn, a SFK, in promoting the survival of human glioblastoma tumor (GBM) cells in vitro and in vivo using lentiviral vector-mediated expression of constitutively-active Lyn (CA-Lyn) or dominant-negative Lyn (DN-Lyn). Expression of either CA-Lyn or DN-Lyn had no effect on the survival of U87 GBM cells grown under nutrient-rich conditions. In contrast, under nutrient-deprived conditions (absence of supplementation with L-glutamine, which is essential for growth of GBM cells, and FBS) CA-Lyn expression enhanced survival and promoted autophagy as well as inhibiting cell death and promoting proliferation. Expression of DN-Lyn promoted cell death. In the nutrient-deprived GBM cells, CA-Lyn expression enhanced AMPK activity and reduced the levels of pS6 kinase whereas DN-Lyn enhanced the levels of pS6 kinase. Similar results were obtained in vitro using another cultured GBM cell line and primary glioma stem cells. On propagation of the transduced GBM cells in the brains of nude mice, the CA-Lyn xenografts formed larger tumors than control cells and autophagosomes were detectable in the tumor cells. The DN-Lyn xenografts formed smaller tumors and contained more apoptotic cells. Our findings suggest that on nutrient deprivation in vitro Lyn acts to enhance the survival of GBM cells by promoting autophagy and proliferation as well as inhibiting cell death, and Lyn promotes the same effects in vivo in xenograft tumors. As the levels of Lyn protein or its activity are elevated in several cancers these findings may be of broad relevance to cancer biology. |
| Databáze: | OpenAIRE |
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