Tumour-associated mutant p53 drives the Warburg effect

Cen Zhang, Juan Liu, Yingjian Liang, Rui Wu, Yuhan Zhao, Xuehui Hong, Meihua Lin, Haiyang Yu, Lianxin Liu, Arnold J. Levine, Wenwei Hu () and Zhaohui Feng ()
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Cen Zhang: Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey
Juan Liu: Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey
Yingjian Liang: Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey
Rui Wu: Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey
Yuhan Zhao: Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey
Xuehui Hong: Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey
Meihua Lin: Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey
Haiyang Yu: Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey
Lianxin Liu: Laboratory of Hepatosplenic Surgery, First Affiliated Hospital of Harbin Medical University
Arnold J. Levine: The Institute for Advanced Study
Wenwei Hu: Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey
Zhaohui Feng: Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey

Nature Communications, 2013, vol. 4, issue 1, 1-15

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms3935

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