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- Title
GASDERMIN, suppressed frequently in gastric cancer, is a target of LMO1 in TGF-β-dependent apoptotic signalling.
- Authors
Saeki, N.; Kim, D. H.; Usui, T.; Aoyagi, K.; Tatsuta, T.; Aoki, K.; Yanagihara, K.; Tamura, M.; Mizushima, H.; Sakamoto, H.; Ogawa, K.; Ohki, M.; Shiroishi, T.; Yoshida, T.; Sasaki, H.
- 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.Oncogene (2007) 26, 6488–6498; doi:10.1038/sj.onc.1210475; published online 30 April 2007
- Subjects
APOPTOSIS; EPITHELIUM; CANCER cells; TRANSCRIPTION factors; GASTROINTESTINAL cancer; EPITHELIAL cells
- Publication
Oncogene, 2007, Vol 26, Issue 45, p6488
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1210475