RRC ID 63843
著者 Sano H, Futamura M, Gaowa S, Kamino H, Nakamura Y, Yamaguchi K, Tanaka Y, Yasufuku I, Nakakami A, Arakawa H, Yoshida K.
タイトル p53/Mieap-regulated mitochondrial quality control plays an important role as a tumor suppressor in gastric and esophageal cancers.
ジャーナル Biochem Biophys Res Commun
Abstract Mitochondria-eating protein (Mieap) plays a critical role in mitochondrial quality control (MQC) and functions as a p53-inducible tumor suppressor. This study aimed to examine its role in gastric cancer (GC) and esophageal cancer (EC). GC cells were infected with Mieap-overexpressing adenovirus (Ad-Mieap) and subjected to fluorescence-activated cell sorting (FACS), western blotting, and caspase assays. Thereafter, we evaluated the potential disruption of the p53/Mieap-regulated MQC pathway in vivo. Methylation-specific PCR (MSP) for Mieap, NIX, and BNIP3 promoters was performed and p53 mutations were detected using cryopreserved surgical specimens. Exogenous Mieap in GC cells induced the formation of vacuole-like structures (called MIVs, Mieap-induced vacuoles) and caspase-dependent cell death, with the activation of both caspase-3 and caspase-9. Of the 47 GC patients, promoter methylation in Mieap, BNIP3, and NIX was identified in two (4.3%), 29 (61.7%), and zero (0%) specimens, respectively. In total, 33 GC patients (70.2%) inactivated this MQC pathway. Amazingly, BNIP3 promoter in the normal epithelium was highly methylated in 18 of the 47 GC patients (38.3%). In EC patients, this MQC pathway was also inactivated in ten of 12 patients (83.3%). These results indicate that p53/Mieap-regulated MQC plays an important role in upper gastrointestinal (GI) tumor suppression, possibly, in part, through the mitochondrial apoptotic pathway.
巻・号 529(3)
ページ 582-589
公開日 2020-8-27
DOI 10.1016/j.bbrc.2020.05.168
PII S0006-291X(20)31105-0
PMID 32736677
MeSH Aged Apoptosis / genetics Caspases / metabolism Cell Line, Tumor DNA Methylation Female Gene Expression Regulation, Neoplastic Humans Male Mitochondria / genetics Mitochondria / metabolism* Mitochondrial Proteins / genetics Mitochondrial Proteins / metabolism* Mutation Promoter Regions, Genetic / genetics Signal Transduction / genetics Stomach Neoplasms / genetics Stomach Neoplasms / metabolism* Stomach Neoplasms / pathology Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism* Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism*
IF 2.985
リソース情報
ヒト・動物細胞 MKN1(RCB1003) MKN7(RCB0999) MKN45(RCB1001) MKN74(RCB1002) Kato III(RCB2088) SH-10-TC(RCB1940) TE-1(RCB1894) TE-4(RCB2097) TE-5(RCB1949) TE-10(RCB2099)