title: Regulation of CRADD-caspase 2 cascade by histone deacetylase 1 in gastric cancer.
abstract: CRADD, also referred as RAIDD, is an adaptor protein that could interact with both caspase 2 and RIP that can promote apoptosis once activated. HDAC inhibitors are promising anti-cancer agents by inducing apoptosis of various cancer cells. In this study, we found that CRADD was induced by TSA (trichostatin A) to activate caspase 2-dependent apoptosis. CRADD was downregulated in gastric cancer and the restoration of its expression suppressed the viability of gastric cancer cells. HDAC1 was responsible for its downregulation in gastric cancer since HDAC1 siRNA upregulated CRADD expression and HDAC1 directly bound to the promoter of CRADD. Therefore, the high expression of HDAC1 can downregulate CRADD to confer gastric cancer cells the resistance to caspase 2-dependent apoptosis. HDAC inhibitors, potential anti-cancer drugs under investigation, can promote caspase 2-dependent apoptosis by inducing the expression of CRADD.
authors.affiliation: Department of Medical Oncology, Biomedical Research Center, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University China ; Laboratory of Cancer Biology, Biomedical Research Center, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Department of Medical Oncology, Biomedical Research Center, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University China ; Department of Medical Oncology, Jinhua Guangfu Hospital Jinhua, Zhejiang, China.
authors.forename: Wanfen
authors.initials: W
authors.lastname: Tang
authors.affiliation: Laboratory of Cancer Biology, Biomedical Research Center, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Laboratory of Cancer Biology, Biomedical Research Center, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Feng
authors.affiliation: Laboratory of Cancer Biology, Biomedical Research Center, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University China.
authors.forename: Hongchuan
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Medical Oncology, Biomedical Research Center, Sir Runrun Shaw Hospital, School of Medicine, Zhejiang University China.
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
keywords: CRADD; HDAC1; HDACi; TSA; caspase 2; gastric cancer