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 Celljournal_title
Molecular cellauthors
Liu K,Lee J,Kim JY,Wang L,Tian Y,Chan ST,Cho C,Machida K,Chen D,Ou JJdoi
10.1016/j.molcel.2017.09.022subject
Has Abstractpub_date
2017-10-19 00:00:00pages
281-292.e5issue
2eissn
1097-2765issn
1097-4164pii
S1097-2765(17)30700-1journal_volume
68pub_type
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