期刊
AUTOPHAGY
卷 12, 期 9, 页码 1431-1439出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2016.1190053
关键词
ATG7; autophagy; brain; cancer; glioblastoma; metabolism; RCAS; senescence; tumor
类别
资金
- Goodwin Experimental Therapeutic Centerss fund
- Cycle for Survival fund
- NIH [R01CA166413, R01GM113013, 1F32CA162691]
- Carnegie Trust for the Universities of Scotland Grant
- Cancer Research UK [16243] Funding Source: researchfish
- NATIONAL CANCER INSTITUTE [F32CA162691, R01CA166413, P30CA008748] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM113013] Funding Source: NIH RePORTER
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据