The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Mitophagy Controls the Activities of Tumor Suppressor p53 to Regulate Hepatic Cancer Stem Cells
Open accessAbstract
Summary 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 colocalizes 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 to why autophagy is required to promote hepatocarcinogenesis.
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Cites
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894
Self-citationYoule, R. J., & Narendra, D. P. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3028 · Cited by 3,273
Autophagy-deficient mice develop multiple liver tumors
Takamura, A., Komatsu, M., Hara, T., Sakamoto, A., Kishi, C., Waguri, S., Eishi, Y., Hino, O., Tanaka, K., & Mizushima, N. (2011) · Genes & Development · doi:10.1101/gad.2016211 · Cited by 1,342 · cited 8×
“Autophagy may also function as a tumor promoter to alleviate metabolic stress during tumorigenesis and suppress the expression of tumor suppressors (Guo et al., 2013; Rosenfeldt et al., 2013; Tian et al., 2015), and impairing autophagy can impede hepatocarcinogenesis and prevent benign hepatic tumors from becoming mal…”
BackgroundInfluentialThe role for autophagy in cancer
White, E. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73941 · Cited by 1,332
p53 status determines the role of autophagy in pancreatic tumour development
Rosenfeldt, M. T., O’Prey, J., Morton, J. P., Nixon, C., MacKay, G., Mrowinska, A., Au, A., Rai, T. S., Zheng, L., Ridgway, R., et al. (2013) · Nature · doi:10.1038/nature12865 · Cited by 713
Transcriptional Regulation by P53
Beckerman, R., & Prives, C. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a000935 · Cited by 569 · cited 2×
“These two putative p53 binding motifs resemble the p53 response element, which consists of two tandem p53 recognition sequences that are separated by 0–13 base pairs (Beckerman and Prives, 2010; Lin et al., 2005).”
Backgroundp62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria
Okatsu, K., Saisho, K., Shimanuki, M., Nakada, K., Shitara, H., Sou, Y., Kimura, M., Sato, S., Hattori, N., Komatsu, M., et al. (2010) · Genes to Cells · doi:10.1111/j.1365-2443.2010.01426.x · Cited by 397
Cited by
Autophagy, cancer stem cells and drug resistance
Smith, A. G., & Macleod, K. F. (2019) · The Journal of Pathology · doi:10.1002/path.5222 · Cited by 365
Mitophagy in the pathogenesis and management of disease
Wang, Q., Sun, Y., Li, T. Y., & Auwerx, J. (2026) · Cell Research · doi:10.1038/s41422-025-01203-7 · Cited by 103
Autophagy Regulation on Cancer Stem Cell Maintenance, Metastasis, and Therapy Resistance
Wang, X., Lee, J., & Xie, C. (2022) · Cancers · doi:10.3390/cancers14020381 · Cited by 53
Self-citationZhang, H., Steed, A., Co, M., & Chen, X. (2021) · Cancer Drug Resistance · doi:10.20517/cdr.2021.32 · Cited by 50
Metadata
- Authors
- Liu, K., Lee, J., Kim, J. Y., Wang, L., Tian, Y., Chan, S. T., Cho, C., Machida, K., Chen, D., & Ou, J.-H. J.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2017-10
- Volume
- 68
- Issue
- 2
- Pages
- 281-292.e5
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2761556050
- Cited by
- 245
- References
- 7
- FWCI
- 14.65
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Liu, K., Lee, J., Kim, J. Y., Wang, L., Tian, Y., Chan, S. T., Cho, C., Machida, K., Chen, D., & Ou, J.-H. J. (2017). Mitophagy Controls the Activities of Tumor Suppressor p53 to Regulate Hepatic Cancer Stem Cells. Molecular Cell. https://doi.org/10.1016/j.molcel.2017.09.022
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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