A Transcriptional Regulatory Loop of Master Regulator Transcription Factors, PPARG, and Fatty Acid Synthesis Promotes Esophageal Adenocarcinoma.

ABSTRACT: Although obesity is one of the strongest risk factors for esophageal adenocarcinoma, the molecular mechanisms underlying this association remain unclear. We recently identified four esophageal adenocarcinoma-specific master regulator transcription factors (MRTF) ELF3, KLF5, GATA6, and EHF. In this study, gene-set enrichment analysis of both esophageal adenocarcinoma patient samples and cell line models unbiasedly underscores fatty acid synthesis as the central pathway downstream of three MRTFs (ELF3, KLF5, GATA6). Further characterizations unexpectedly identified a transcriptional feedback loop between MRTF and fatty acid synthesis, which mutually activated each other through the nuclear receptor, PPARG. MRTFs cooperatively promoted PPARG transcription by directly regulating its promoter a

SUBMITTER: Ma S 

PROVIDER: S-EPMC8026506 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature