Autophagy suppresses RIP kinase-dependent necrosis enabling survival to mTOR inhibition.
Ontology highlight
ABSTRACT:
SUBMITTER: Bray K
PROVIDER: S-EPMC3406086 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
Publications
Autophagy suppresses RIP kinase-dependent necrosis enabling survival to mTOR inhibition.
Bray Kevin K Mathew Robin R Lau Alexandria A Kamphorst Jurre J JJ Fan Jing J Chen Jim J Chen Hsin-Yi HY Ghavami Anahita A Stein Mark M DiPaola Robert S RS Zhang Donna D Rabinowitz Joshua D JD White Eileen E
PloS one 20120726 7
mTOR inhibitors are used clinically to treat renal cancer but are not curative. Here we show that autophagy is a resistance mechanism of human renal cell carcinoma (RCC) cell lines to mTOR inhibitors. RCC cell lines have high basal autophagy that is required for survival to mTOR inhibition. In RCC4 cells, inhibition of mTOR with CCI-779 stimulates autophagy and eliminates RIP kinases (RIPKs) and this is blocked by autophagy inhibition, which induces RIPK- and ROS-dependent necroptosis in vitro a ...[more]
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