期刊
ACS CHEMICAL BIOLOGY
卷 10, 期 7, 页码 1616-1623出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschembio.5b00240
关键词
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资金
- National Institutes of Health [R01CA172667]
- American Cancer Society Research Scholar Award [RSG14-242-01-TBE]
- DOD Breakthroughs Award
- Searle Scholar Foundation
Fatty acid synthase (FASN) generates the de novo source of lipids for cell proliferation and is a promising cancer therapy target. Development of FASN inhibitors, however, necessitates a better understanding of sensitive and resistant cancer types to optimize patient treatment. Indeed, testing the cytotoxic effects of FASN inhibition across human cancer cells revealed diverse sensitivities. We show here that metabolic incorporation of glucose into specific complex lipid species strongly predicts FASN inhibitor sensitivity. We also show that the levels of one of these lipid classes, protein kinase C (PKC) stimulator diacylglycerols, are lowered upon FASN inhibitor treatment in sensitive compared to resistant cells and that PKC activators and inhibitors rescue cell death in sensitive cells and sensitize resistant cells, respectively. Our findings not only reveal a biomarker for predicting FASN sensitivity in cancer cells but also a put forth a heretofore unrecognized mechanism underlying the anticancer effects of FASN inhibitors.
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