GASDERMIN, suppressed frequently in gastric cancer, is a target of LMO1 in TGF-β-dependent apoptotic signalling
Open Access
- 30 April 2007
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 26 (45), 6488-6498
- https://doi.org/10.1038/sj.onc.1210475
Abstract
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-β receptor (TGF-βRII) in the pit cells, and found that TGF-β 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-β, LMO1, possibly RUNX3, and GSDM form a regulatory pathway for directing the pit cells to apoptosis.Keywords
This publication has 23 references indexed in Scilit:
- Hedgehog Signal Activation in Gastric Pit Cell and in Diffuse-Type Gastric CancerGastroenterology, 2006
- Comment on Levanon et al., ‘Runx3 knockouts and stomach cancer’, in EMBO reports (June 2003)EMBO Reports, 2003
- A faithful method for PCR-mediated global mRNA amplification and its integration into microarray analysis on laser-captured cellsBiochemical and Biophysical Research Communications, 2002
- Identification and characterization of LMO 4 , an LMO gene with a novel pattern of expression during embryogenesisProceedings of the National Academy of Sciences of the United States of America, 1998
- Thrombospondin-1 Is a Major Activator of TGF-β1 In VivoCell, 1998
- Establishment of lymph node metastatic model for human gastric cancer in nude mice and analysis of factors associated with metastasisClinical & Experimental Metastasis, 1997
- Expression cloning of gastric mucin complementary DNA and localization of mucin gene expressionGastroenterology, 1995
- MUC6 apomucin shows a distinct normal tissue distribution that correlates with Lewis antigen expression in the human stomachGastroenterology, 1995
- Origin and migratory pathways of the eleven epithelial cell types present in the body of the mouse stomachMicroscopy Research and Technique, 1995
- The rhombotin gene family encode related LIM-domain proteins whose differing expression suggests multiple roles in mouse developmentJournal of Molecular Biology, 1992