SREBP1 regulates mitochondrial metabolism in oncogenic KRAS expressing NSCLC [preprint]
UMass Chan AffiliationsProgram in Molecular Medicine
non-small cell lung cancer
Biochemical Phenomena, Metabolism, and Nutrition
Cellular and Molecular Physiology
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AbstractCancer cells require extensive metabolic reprogramming in order to provide the bioenergetics and macromolecular precursors needed to sustain a malignant phenotype. Mutant KRAS is a driver oncogene that is well known for its ability to regulate the ERK and PI3K signaling pathways. However, it is now appreciated that KRAS can promote tumor growth via upregulation of anabolic metabolism. We recently showed that oncogenic KRAS promotes a gene expression program of de novo lipogenesis in non-small cell lung cancer (NSCLC). To define the mechanism(s) responsible, we focused on the lipogenic transcription factor SREBP1. We observed that KRAS increases SREBP1 expression and genetic knockdown of SREBP1 significantly inhibited cell proliferation of mutant KRAS-expressing cells. Unexpectedly, lipogenesis was not significantly altered in cells subject to SREBP1 knockdown. Carbon tracing metabolic studies showed a significant decrease in oxidative phosphorylation and RNA-seq data revealed a significant decrease in mitochondrial encoded subunits of the electron transport chain (ETC). Taken together, these data support a novel role, distinct from lipogenesis, of SREBP1 on mitochondrial function in mutant KRAS NSCLC.
bioRxiv 2020.01.15.896373; doi: https://doi.org/10.1101/2020.01.15.896373. Link to preprint on bioRxiv service.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/29428
RightsThe copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-ND 4.0 International license.
Except where otherwise noted, this item's license is described as The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-ND 4.0 International license.