Mutant p53 controls tumor metabolism and metastasis by regulating PGC-1α
| العنوان: | Mutant p53 controls tumor metabolism and metastasis by regulating PGC-1α |
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| المؤلفون: | Qing Chen, Jeremy P. Scott, Subhasree Basu, Michele Tavecchio, Andrew V. Kossenkov, Maureen E. Murphy, Thibaut Barnoud, Che-Pei Kung, Andrea Watters, Keerthana Gnanapradeepan |
| المصدر: | Genes & Development. 32:230-243 |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, chemistry.chemical_classification, Mutant, Tumor cells, Metabolism, Oxidative phosphorylation, Biology, medicine.disease, Amino acid, Metastasis, 03 medical and health sciences, 030104 developmental biology, Gain of function, chemistry, Codon 72 polymorphism, Genetics, Cancer research, medicine, Developmental Biology |
| الوصف: | 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. |
| تدمد: | 1549-5477 0890-9369 |
| DOI: | 10.1101/gad.309062.117 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::d311ba7a82a82b71174e54191d3b3ec8 https://doi.org/10.1101/gad.309062.117 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi...........d311ba7a82a82b71174e54191d3b3ec8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15495477 08909369 |
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| DOI: | 10.1101/gad.309062.117 |