Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis.

Abstract

Defective apoptosis renders immortalized epithelial cells highly tumorigenic, but how this is impacted by other common tumor mutations is not known. In apoptosis-defective cells, inhibition of autophagy by AKT activation or by allelic disruption of beclin1 confers sensitivity to metabolic stress by inhibiting an autophagy-dependent survival pathway. While autophagy acts to buffer metabolic stress, the combined impairment of apoptosis and autophagy promotes necrotic cell death in vitro and in vivo. Thus, inhibiting autophagy under conditions of nutrient limitation can restore cell death to apoptosis-refractory tumors, but this necrosis is associated with inflammation and accelerated tumor growth. Thus, autophagy may function in tumor suppression by mitigating metabolic stress and, in concert with apoptosis, by preventing death by necrosis.

DOI: 10.1016/j.ccr.2006.06.001

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@article{Degenhardt2006AutophagyPT, title={Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis.}, author={Kurt Degenhardt and Robin Mathew and Brian L. Beaudoin and Kevin Bray and Diana Anderson and Guanghua Jim Chen and Chandreyee Mukherjee and Yufang Shi and C{\'e}line G{\'e}linas and Yongjun Fan and Deirdre A. Nelson and Shengkan V Jin and Eileen P. White}, journal={Cancer cell}, year={2006}, volume={10 1}, pages={51-64} }