Tissue-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.

To translate our findings to human cancer, we analyzed The Cancer Genome Atlas RNA-Seq data and identified a highly significant positive correlation between FASN and CS gene expression in human colon adenocarcinomas ( Figure 6 C).

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We noted that other TCA cycle substrates such as malate and fumarate are also decreased in FASN +/∆ /Apc/Cre and FASN ∆/∆ /Apc/Cre mice as compared to Apc/Cre mice, but these changes did not reach statistical significance ( Figure 5 D).Even though the level of citrate significantly decreased, the expression of CS increased, potentially due to feedback regulation by the availability of the precursor pyruvate (thus acetyl CoA) ( Figure 5 A,C and Table S3 ).

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