Mitophagy Controls the Activities of Tumor Suppressor p53 to Regulate Hepatic Cancer Stem Cells.

Abstract:

:Autophagy is required for benign hepatic tumors to progress into malignant hepatocellular carcinoma. However, the mechanism is unclear. Here, we report that mitophagy, the selective removal of mitochondria by autophagy, positively regulates hepatic cancer stem cells (CSCs) by suppressing the tumor suppressor p53. When mitophagy is enhanced, p53 co-localizes with mitochondria and is removed by a mitophagy-dependent manner. However, when mitophagy is inhibited, p53 is phosphorylated at serine-392 by PINK1, a kinase associated with mitophagy, on mitochondria and translocated into the nucleus, where it binds to the NANOG promoter to prevent OCT4 and SOX2 transcription factors from activating the expression of NANOG, a transcription factor critical for maintaining the stemness and the self-renewal ability of CSCs, resulting in the reduction of hepatic CSC populations. These results demonstrate that mitophagy controls the activities of p53 to maintain hepatic CSCs and provide an explanation as to why autophagy is required to promote hepatocarcinogenesis.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Liu K,Lee J,Kim JY,Wang L,Tian Y,Chan ST,Cho C,Machida K,Chen D,Ou JJ

doi

10.1016/j.molcel.2017.09.022

subject

Has Abstract

pub_date

2017-10-19 00:00:00

pages

281-292.e5

issue

2

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(17)30700-1

journal_volume

68

pub_type

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