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Tumor suppressor Parkin induces p53-mediated cell cycle arrest in human lung and colorectal cancer cells

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Dysregulation of the E3 ubiquitin ligase Parkin has been linkedto various human cancers, indicating that Parkin is a tumorsuppressor protein. However, the mechanisms of action ofParkin remain unclear to date. Thus, we aimed to elucidate themechanisms of action of Parkin as a tumor suppressor in humanlung and colorectal cancer cells. Results showed that Parkinoverexpression reduced the viability of A549 human lung cancercells by inducing G2/M cell cycle arrest. In addition, Parkincaused DNA damage and ATM (Ataxia telangiectasia mutated)activation, which subsequently led to p53 activation. It alsoinduced the p53-mediated upregulation of p21 and downregulationof cyclin B1. Moreover, Parkin suppressed the proliferationof HCT-15 human colorectal cancer cells by a mechanismsimilar to that in A549 lung cancer cells. Taken together, ourresults suggest that the tumor-suppressive effects of Parkin onlung and colorectal cancer cells are mediated by DNA damage/p53 activation/cyclin B1 reduction/cell cycle arrest.

Abstract

Dysregulation of the E3 ubiquitin ligase Parkin has been linkedto various human cancers, indicating that Parkin is a tumorsuppressor protein. However, the mechanisms of action ofParkin remain unclear to date. Thus, we aimed to elucidate themechanisms of action of Parkin as a tumor suppressor in humanlung and colorectal cancer cells. Results showed that Parkinoverexpression reduced the viability of A549 human lung cancercells by inducing G2/M cell cycle arrest. In addition, Parkincaused DNA damage and ATM (Ataxia telangiectasia mutated)activation, which subsequently led to p53 activation. It alsoinduced the p53-mediated upregulation of p21 and downregulationof cyclin B1. Moreover, Parkin suppressed the proliferationof HCT-15 human colorectal cancer cells by a mechanismsimilar to that in A549 lung cancer cells. Taken together, ourresults suggest that the tumor-suppressive effects of Parkin onlung and colorectal cancer cells are mediated by DNA damage/p53 activation/cyclin B1 reduction/cell cycle arrest.

참고문헌 (41)

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