Tumour-associated mutant p53 drives the Warburg effect

Nature Communications
Cen ZhangZhaohui Feng

Abstract

Tumour cells primarily utilize aerobic glycolysis for energy production, a phenomenon known as the Warburg effect. Its mechanism is not well understood. The tumour suppressor gene p53 is frequently mutated in tumours. Many tumour-associated mutant p53 (mutp53) proteins not only lose tumour suppressive function but also gain new oncogenic functions that are independent of wild-type p53, defined as mutp53 gain of function (GOF). Here we show that tumour-associated mutp53 stimulates the Warburg effect in cultured cells and mutp53 knockin mice as a new mutp53 GOF. Mutp53 stimulates the Warburg effect through promoting GLUT1 translocation to the plasma membrane, which is mediated by activated RhoA and its downstream effector ROCK. Inhibition of RhoA/ROCK/GLUT1 signalling largely abolishes mutp53 GOF in stimulating the Warburg effect. Furthermore, inhibition of glycolysis in tumour cells greatly compromises mutp53 GOF in promoting tumorigenesis. Thus, our results reveal a new mutp53 GOF and a mechanism for controlling the Warburg effect.

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Methods Mentioned

BETA
flow cytometry
GTPase
xenograft
Assay
PCR
pull-down

Software Mentioned

GraphPad Prism

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