GASDERMIN, suppressed frequently in gastric cancer, is a target of LMO1 in TGF-beta-dependent apoptotic signalling

Oncogene. 2007 Oct 4;26(45):6488-98. doi: 10.1038/sj.onc.1210475. Epub 2007 Apr 30.


Defining apoptosis-regulatory cascades of the epithelium is important for understanding carcinogenesis, since cancer cells are considered to arise as a result of the collapse of the cascades. We previously reported that a novel gene GASDERMIN (GSDM) is expressed in the stomach but suppressed in gastric cancer cell lines. Furthermore, in this study, we demonstrated that GSDM is expressed in the mucus-secreting pit cells of the gastric epithelium and frequently silenced in primary gastric cancers. We found that GSDM has a highly apoptotic activity and its expression is regulated by a transcription factor LIM domain only 1 (LMO1) through a sequence to which Runt-related transcription factor 3 (RUNX3) binds, in a GSDM promoter region. We observed coexpression of GSDM with LMO1, RUNX3 and type II transforming growth factor-beta receptor (TGF-betaRII) in the pit cells, and found that TGF-beta upregulates the LMO1- and GSDM-expression in the gastric epithelial cell line and induces apoptosis, which was confirmed by the finding that the apoptosis induction is inhibited by suppression of each LMO1-, RUNX3- and GSDM expression, respectively. The present data suggest that TGF-beta, LMO1, possibly RUNX3, and GSDM form a regulatory pathway for directing the pit cells to apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Base Sequence
  • Cell Line, Tumor
  • Core Binding Factor Alpha 3 Subunit / physiology
  • DNA-Binding Proteins / physiology*
  • Gastric Mucosa / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • LIM Domain Proteins
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics*
  • Promoter Regions, Genetic
  • Signal Transduction*
  • Stomach Neoplasms / genetics*
  • Transcription Factors / physiology*
  • Transcription Initiation Site
  • Transforming Growth Factor beta / metabolism*


  • Core Binding Factor Alpha 3 Subunit
  • DNA-Binding Proteins
  • GSDMA protein, human
  • LIM Domain Proteins
  • LMO1 protein, human
  • Neoplasm Proteins
  • Runx3 protein, human
  • Transcription Factors
  • Transforming Growth Factor beta