University of Massachusetts Medical School Faculty Publications
UMMS Affiliation
Program in Molecular Medicine
Publication Date
2020-01-15
Document Type
Article Preprint
Disciplines
Biochemical Phenomena, Metabolism, and Nutrition | Cancer Biology | Cellular and Molecular Physiology
Abstract
Cancer 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.
Keywords
Cancer Biology, SREBP1, non-small cell lung cancer, transcription factors, KRAS
Rights and Permissions
The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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.
DOI of Published Version
10.1101/2020.01.15.896373
Source
bioRxiv 2020.01.15.896373; doi: https://doi.org/10.1101/2020.01.15.896373. Link to preprint on bioRxiv service.
Journal/Book/Conference Title
bioRxiv
Repository Citation
Ruiz CF, Montal ED, Haley JA, Haley JD. (2020). SREBP1 regulates mitochondrial metabolism in oncogenic KRAS expressing NSCLC. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/2020.01.15.896373. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1655
Creative Commons License
This work is licensed under a Creative Commons Attribution-No Derivative Works 4.0 License.
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Cancer Biology Commons, Cellular and Molecular Physiology Commons