biostudies-literatureDrury JRally Foundation Independent Investigator GrantSt. Baldrick's Career Development AwardNIA NIH HHSNCI NIH HHSNINDS NIH HHSV-Scholar GrantNIGMS NIH HHSNIH HHS6510https://www.ebi.ac.uk/biostudies/studies/S-EPMC9245602biostudies-literatureUnknown23(12)Altered lipid metabolism is a potential target for therapeutic intervention in cancer. Overexpression of Fatty Acid Synthase (FASN) correlates with poor prognosis in colorectal cancer (CRC). While multiple studies show that upregulation of lipogenesis is critically important for CRC progression, the contribution of FASN to CRC initiation is poorly understood. We utilize a C57BL/6-Apc/Villin-Cre mouse model with knockout of FASN in intestinal epithelial cells to show that the heterozygous deletion of FASN increases mouse survival and decreases the number of intestinal adenomas. Using RNA-Seq and gene set enrichment analysis, we demonstrate that a decrease in FASN expression is associated with inhibition of pathways involved in cellular proliferation, energy production, and CRC progression. International journal of molecular sciencesTissue-Specific Downregulation of Fatty Acid Synthase Suppresses Intestinal Adenoma Formation via Coordinated Reprograming of Transcriptome and Metabolism in the Mouse Model of Apc-Driven Colorectal Cancer.PMC9245602P30 CA177558R01 AG066653R01 CA249734, R03 CA262720n/aR35 NS116824P20 GM121327R01 CA249734R03 CA262720Liu JHe DWang CZaytseva YYDrury JFan TGentry MSScott TLYoung LEASun RWeiss HLKelson COWu YfalseTissue-Specific Downregulation of Fatty Acid Synthase Suppresses Intestinal Adenoma Formation via Coordinated Reprograming of Transcriptome and Metabolism in the Mouse Model of Apc-Driven Colorectal Cancer.Altered lipid metabolism is a potential target for therapeutic intervention in cancer. Overexpression of Fatty Acid Synthase (FASN) correlates with poor prognosis in colorectal cancer (CRC). While multiple studies show that upregulation of lipogenesis is critically important for CRC progression, the contribution of FASN to CRC initiation is poorly understood. We utilize a C57BL/6-Apc/Villin-Cre mouse model with knockout of FASN in intestinal epithelial cells to show that the heterozygous deletion of FASN increases mouse survival and decreases the number of intestinal adenomas. Using RNA-Seq and gene set enrichment analysis, we demonstrate that a decrease in FASN expression is associated with inhibition of pathways involved in cellular proliferation, energy production, and CRC progression. 2022-01-01T00:00:00Z2022 Jun2025-05-18T12:47:13.463Z2022-07-08T23:09:49.471ZS-EPMC92456023574295310.3390/ijms23126510