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Fats and Mets, KRAS-Driven Lipid Dysregulation Affects Metastatic Potential in Pancreatic Cancer


In this issue of Cancer Research, Rozeveld and colleagues present intriguing evidence of the importance of lipid droplets and hormone-sensitive lipase (HSL) in regulating the aggressive nature of pancreatic cancer. Initially demonstrating a dependency of preloaded lipids on an invasive phenotype, the authors then establish that oncogenic KRAS mutation downregulates HSL, thereby facilitating lipid storage during steady state. Thereafter, a phenotypic switch to oxidative metabolism with lipid utilization to fuel invasion and metastasis occurs. Experimentally, blocking the KRAS-HSL axis results in fewer lipid droplets, as well as metabolic reprogramming of the invasive cell phenotype, effectively reducing invasive capacity of KRAS-mutant pancreatic cancer. Of note, HSL overexpression in tumor cells also inhibited invasion, due to depletion of lipid droplets and the stored lipids, which are essential during invasion. Collectively, these novel findings highlight the importance of energy metabolism and its dynamic regulation in the evolution of the metastatic capacity of pancreatic cancer.See related article by Rozeveld et al., p. 4932.

Type Journal
ISBN 1538-7445 (Electronic) 0008-5472 (Linking)
Authors Man, J.; Pajic, M.; Joshua, A. M.
Responsible Garvan Author A/Prof Marina Pajic
Published Date 2020-11-30
Published Volume 80
Published Issue 22
Published Pages 4886-4887
Status Published in-print
DOI 10.1158/0008-5472.CAN-20-3082
URL link to publisher's version