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Tumour-associated mutant p53 drives the Warburg effect

Author(s): Zhang, Cen; Liu, Juan; Liang, Yingjian; Wu, Rui; Zhao, Yuhan; et al

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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.
Publication Date: Dec-2013
Electronic Publication Date: 17-Dec-2013
Citation: Zhang, Cen, Liu, Juan, Liang, Yingjian, Wu, Rui, Zhao, Yuhan, Hong, Xuehui, Lin, Meihua, Yu, Haiyang, Liu, Lianxin, Levine, Arnold J, Hu, Wenwei, Feng, Zhaohui. (2013). Tumour-associated mutant p53 drives the Warburg effect. Nature Communications, 4 (1), doi:10.1038/ncomms3935
DOI: doi:10.1038/ncomms3935
EISSN: 2041-1723
Pages: 1 - 15
Type of Material: Journal Article
Journal/Proceeding Title: Nature Communications
Version: Final published version. This is an open access article.

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