Inhibition of adipose triglyceride lipase (ATGL) by the putative tumor suppressor G0S2 or a small molecule inhibitor attenuates the growth of cancer cells
PDF | HTML | How to cite
Metrics: PDF 2185 views | HTML 3180 views | ?
Rachid Zagani1, Wissal El-Assaad1, Isabelle Gamache1 and Jose G. Teodoro1,2
1 Goodman Cancer Research Centre, McGill University, Montréal, QC, Canada
2 Department of Biochemistry, McGill University, Montréal, QC, Canada
Jose G. Teodoro, email:
Keywords: lipase, ATGL, G0S2, metabolism, lipids, triglycerides, tumor suppressor
Received: January 22, 2015 Accepted: July 03, 2015 Published: July 31, 2015
The G0/G1 switch gene 2 (G0S2) is methylated and silenced in a wide range of human cancers. The protein encoded by G0S2 is an endogenous inhibitor of lipid catabolism that directly binds adipose triglyceride lipase (ATGL). ATGL is the rate-limiting step in triglyceride metabolism. Although the G0S2 gene is silenced in cancer, the impact of ATGL in the growth and survival of cancer cells has never been addressed. Here we show that ectopic expression of G0S2 in non-small cell lung carcinomas (NSCL) inhibits triglyceride catabolism and results in lower cell growth. Similarly, knockdown of ATGL increased triglyceride levels, attenuated cell growth and promoted apoptosis. Conversely, knockdown of endogenous G0S2 enhanced the growth and invasiveness of cancer cells. G0S2 is strongly induced in acute promyelocytic leukemia (APL) cells in response to all trans retinoic acid (ATRA) and we show that inhibition of ATGL in these cells by G0S2 is required for efficacy of ATRA treatment. Our data uncover a novel tumor suppressor mechanism by which G0S2 directly inhibits activity of a key intracellular lipase. Our results suggest that elevated ATGL activity may be a general property of many cancer types and potentially represents a novel target for chemotherapy.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.