TGIF1

Overview

TGIF1 (TGF-beta-Induced Factor Homeobox 1) encodes a homeodomain transcription factor that acts as a transcriptional co-repressor in TGF-beta signaling, recruiting histone deacetylases (HDACs) to repress SMAD-dependent target genes. By limiting TGF-beta-mediated growth arrest, TGIF1 overexpression or gain-of-function can promote oncogenesis. TGIF1 is also involved in retinoic acid signaling. Its mutations in colorectal cancer implicate TGF-beta pathway dysregulation as a driver mechanism.

Alterations observed in the corpus

  • Newly nominated TGF-beta signaling co-repressor driver gene in colorectal cancer (CRC), identified in a large CRC exome-sequencing and neoantigen analysis of 619 cases PMID:27149842.

Cancer types (linked)

  • COAD / Colorectal cancer: Newly identified as a significantly mutated CRC driver gene in the TGF-beta pathway PMID:27149842.

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • TGF-beta pathway inhibition is under active investigation in gastrointestinal cancers; whether TGIF1 mutations confer sensitivity or resistance to TGF-beta-directed therapies was not addressed in the citing study PMID:27149842.

Open questions

  • The functional consequence (gain vs. loss of function) of TGIF1 mutations in CRC was not determined in the citing study PMID:27149842.

Sources

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