PLX063936

GSE109373: Mutant p53 controls tumor metabolism and metastasis by regulating PGC-1

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Mutant forms of p53 protein often possess pro-tumorigenic function, conferring increased survival and migration to tumor cells via its gain of function activity. Whether and how a common polymorphism in TP53 at amino acid 72 (Pro72Arg, hereafter 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-1, and that this regulation is markedly impacted by the codon 72 polymorphism. Tumor cells with the R72 variant of mutant p53 show increased PGC-1 function, along with greatly increased mitochondrial function and metastatic capability. Breast cancers containing mutant p53 and the R72 variant show poorer prognosis compared to P72. The combined results reveal PGC-1 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. SOURCE: Priyankara,J,Wickramasinghe (priyaw@wistar.org) - Genomics The Wistar Institute