TY - JOUR
T1 - Effect of mutant p53 proteins on glycolysis and mitochondrial metabolism
AU - Eriksson, Matilda
AU - Ambroise, Gorbatchev
AU - Ouchida, Amanda Tomie
AU - Queiroz, Andre Lima
AU - Smith, Dominique
AU - Gimenez-Cassina, Alfredo
AU - Iwanicki, Marcin P.
AU - Muller, Patricia A.
AU - Norberg, Erik
AU - Vakifahmetoglu-Norberg, Helin
N1 - Publisher Copyright:
© 2017 American Society for Microbiology.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - TP53 is one of the most commonly mutated genes in human cancers. Unlike other tumor suppressors that are frequently deleted or acquire lossof- function mutations, the majority of TP53 mutations in tumors are missense substitutions, which lead to the expression of full-length mutant proteins that accumulate in cancer cells and may confer unique gain-of-function (GOF) activities to promote tumorigenic events. Recently, mutant p53 proteins have been shown to mediate metabolic changes as a novel GOF to promote tumor development. There is a strong rationale that the GOF activities, including alterations in cellular metabolism, might vary between the different p53 mutants. Accordingly, the effect of different mutant p53 proteins on cancer cell metabolism is largely unknown. In this study, we have metabolically profiled several individual frequently occurring p53 mutants in cancers, focusing on glycolytic and mitochondrial oxidative phosphorylation pathways. Our investigation highlights the diversity of different p53 mutants in terms of their effect on metabolism, which might provide a foundation for the development of more effective targeted pharmacological approaches toward variants of mutant p53.
AB - TP53 is one of the most commonly mutated genes in human cancers. Unlike other tumor suppressors that are frequently deleted or acquire lossof- function mutations, the majority of TP53 mutations in tumors are missense substitutions, which lead to the expression of full-length mutant proteins that accumulate in cancer cells and may confer unique gain-of-function (GOF) activities to promote tumorigenic events. Recently, mutant p53 proteins have been shown to mediate metabolic changes as a novel GOF to promote tumor development. There is a strong rationale that the GOF activities, including alterations in cellular metabolism, might vary between the different p53 mutants. Accordingly, the effect of different mutant p53 proteins on cancer cell metabolism is largely unknown. In this study, we have metabolically profiled several individual frequently occurring p53 mutants in cancers, focusing on glycolytic and mitochondrial oxidative phosphorylation pathways. Our investigation highlights the diversity of different p53 mutants in terms of their effect on metabolism, which might provide a foundation for the development of more effective targeted pharmacological approaches toward variants of mutant p53.
KW - Cancer
KW - EMT
KW - Glycolysis
KW - Metabolism
KW - Mutant p53
KW - OxPhos
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U2 - 10.1128/MCB.00328-17
DO - 10.1128/MCB.00328-17
M3 - Article
C2 - 28993478
AN - SCOPUS:85035762472
SN - 0270-7306
VL - 37
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 24
M1 - e00328-17
ER -