Mieap-regulated mitochondrial quality control is frequently inactivated in human colorectal cancer

• DOI: 10.1038/oncsis.2015.43
• Publication Date: 2016-01-04T14:22:44Z
• Authors: H Kamino; Y Nakamura; M Tsuneki; H Sano; Y Miyamoto; N Kitamura; M Futamura; Y Kanai; H Taniguchi; D Shida; Y Kanemitsu; Y Moriya; K Yoshida; H Arakawa
• Keywords: 0301 basic medicine; 0303 health sciences; 03 medical and health sciences; Original Article; 3. Good health

Mieap, a p53-inducible protein, controls mitochondrial quality by repairing or eliminating unhealthy mitochondria. BNIP3 and NIX are critical mediators for the Mieap-regulated control. Mieap suppresses murine intestinal tumor via its control function. To explore role of mitochondria function in colorectal cancer patients, we examined statuses p53, 57 primary tissues. Promoter methylation genes was found 9% 47% cases, respectively, whereas p53 mutation more than 50% tissues lacking promoters, implying that p53/Mieap/BNIP3-regulated pathway is inactivated 70% patients. In LS174T cells, hypoxia activated Knockdown cells severely impaired hypoxia-activated function, leading to accumulation increase reactive oxygen species generation. The generated p53/Mieap/BNIP3-deficient remarkably enhanced cell migration invasion under hypoxic condition. These results suggest has suppression vivo microenvironment.