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Mutant p53 controls tumor metabolism and metastasis by regulating PGC-1α.
- Source :
-
Genes & development [Genes Dev] 2018 Feb 01; Vol. 32 (3-4), pp. 230-243. Date of Electronic Publication: 2018 Feb 20. - Publication Year :
- 2018
-
Abstract
- Mutant forms of p53 protein often possess protumorigenic functions, conferring increased survival and migration to tumor cells via their "gain-of-function" activity. Whether and how a common polymorphism in TP53 at amino acid 72 (Pro72Arg; referred to here as P72 and R72) impacts this gain of function has not been determined. We show that mutant p53 enhances migration and metastasis of tumors through the ability to bind and regulate PGC-1α and that this regulation is markedly impacted by the codon 72 polymorphism. Tumor cells with the R72 variant of mutant p53 show increased PGC-1α function along with greatly increased mitochondrial function and metastatic capability. Breast cancers containing mutant p53 and the R72 variant show poorer prognosis compared with P72. The combined results reveal PGC-1α as a novel "gain-of-function" partner of mutant p53 and indicate that the codon 72 polymorphism influences the impact of mutant p53 on metabolism and metastasis.<br /> (© 2018 Basu et al.; Published by Cold Spring Harbor Laboratory Press.)
- Subjects :
- Animals
Breast Neoplasms genetics
Breast Neoplasms metabolism
Breast Neoplasms mortality
Cell Line, Tumor
Cell Movement
Female
Hepatocyte Nuclear Factor 4 metabolism
Humans
Male
Mice
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasms genetics
Neoplasms pathology
Oxidative Phosphorylation
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha antagonists & inhibitors
Genes, p53
Mutation
Neoplasms metabolism
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1549-5477
- Volume :
- 32
- Issue :
- 3-4
- Database :
- MEDLINE
- Journal :
- Genes & development
- Publication Type :
- Academic Journal
- Accession number :
- 29463573
- Full Text :
- https://doi.org/10.1101/gad.309062.117