GASDERMIN, suppressed frequently in gastric cancer, is a target of LMO1 in TGF-β-dependent apoptotic signalling
| Autor: | Kazuhiko Aoyagi, T Tatsuta, K Ogawa, K Aoki, D H Kim, T Shiroishi, Kazuyoshi Yanagihara, Hideo Sasaki, Hiromi Sakamoto, M Tamura, T Usui, H Mizushima, N Saeki, Teruhiko Yoshida, Misao Ohki |
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| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Molecular Sequence Data Apoptosis Biology medicine.disease_cause Growth factor receptor Stomach Neoplasms Transforming Growth Factor beta Cell Line Tumor TGF beta signaling pathway Genetics medicine Humans Promoter Regions Genetic Molecular Biology Transcription factor Base Sequence LIM Domain Proteins Cell cycle digestive system diseases Neoplasm Proteins DNA-Binding Proteins Gene Expression Regulation Neoplastic Core Binding Factor Alpha 3 Subunit Gastric Mucosa Cancer cell Cancer research Transcription Initiation Site Carcinogenesis Signal Transduction Transcription Factors Transforming growth factor |
| Zdroj: | Oncogene. 26:6488-6498 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1210475 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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