Tumour-associated Mutant P53 Drives the Warburg Effect

Overview

Journal Nat Commun

Specialty Biology

Date 2013 Dec 18

PMID 24343302

Citations 256

Authors

Cen Zhang

Juan Liu

Yingjian Liang

Rui Wu

Yuhan Zhao

Xuehui Hong

Meihua Lin

Haiyang Yu

Lianxin Liu

Arnold J Levine

Wenwei Hu

Zhaohui Feng

Affiliations

Soon will be listed here.

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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