Suppression of autophagy impedes glioblastoma development and induces senescence Journal Article
| Authors: | Gammoh, N.; Fraser, J.; Puente, C.; Syred, H. M.; Kang, H.; Ozawa, T.; Lam, D.; Acosta, J. C.; Finch, A. J.; Holland, E.; Jiang, X. |
| Article Title: | Suppression of autophagy impedes glioblastoma development and induces senescence |
| Abstract: | The function of macroautophagy/autophagy during tumor initiation or in established tumors can be highly distinct and context-dependent. To investigate the role of autophagy in gliomagenesis, we utilized a KRAS-driven glioblastoma mouse model in which autophagy is specifically disrupted via RNAi against Atg7, Atg13 or Ulk1. Inhibition of autophagy strongly reduced glioblastoma development, demonstrating its critical role in promoting tumor formation. Further supporting this finding is the observation that tumors originating from Atg7-shRNA injections escaped the knockdown effect and thereby still underwent functional autophagy. In vitro, autophagy inhibition suppressed the capacity of KRAS-expressing glial cells to form oncogenic colonies or to survive low serum conditions. Molecular analyses revealed that autophagy-inhibited glial cells were unable to maintain active growth signaling under growth-restrictive conditions and were prone to undergo senescence. Overall, these results demonstrate that autophagy is crucial for glioma initiation and growth, and is a promising therapeutic target for glioblastoma treatment. © 2016 Taylor & Francis. |
| Keywords: | metabolism; brain; glioblastoma; senescence; tumor; autophagy; atg7; cancer; rcas |
| Journal Title: | Autophagy |
| Volume: | 12 |
| Issue: | 9 |
| ISSN: | 1554-8627 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2016-01-01 |
| Start Page: | 1431 |
| End Page: | 1439 |
| Language: | English |
| DOI: | 10.1080/15548627.2016.1190053 |
| PROVIDER: | scopus |
| PUBMED: | 27304681 |
| PMCID: | PMC5082770 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 October 2016 -- Source: Scopus |
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