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Genes Dev. 2018 Feb 1;32(3-4):230-243. doi: 10.1101/gad.309062.117. Epub 2018 Feb 20.

Mutant p53 controls tumor metabolism and metastasis by regulating PGC-1α.

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Program in Molecular and Cellular Oncogenesis, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Graduate Group in Biochemistry and Biophysics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104.
Program in Tumor Microenvironment and Metastasis, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Program in Center for Systems and Computational Biology, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Contributed equally


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.


PGC-1α; codon 72; metastasis; mutant p53; oxidative phosphorylation

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