TAp73-induced phosphofructokinase-1 transcription promotes the Warburg effect and enhances cell proliferation

Le Li, Lijia Li, Wei Li, Taiqi Chen, Bin Zou, Lina Zhao, Huili Wang, Xueying Wang, Lina Xu, Xiaohui Liu, Dong Wang, Bo Li, Tak W. Mak, Wenjing Du (), Xiaolu Yang () and Peng Jiang ()
Additional contact information
Le Li: Tsinghua University; Collaborative Innovation Center for Cancer Medicine
Lijia Li: Tsinghua University; Collaborative Innovation Center for Cancer Medicine
Wei Li: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College
Taiqi Chen: Tsinghua University; Collaborative Innovation Center for Cancer Medicine
Bin Zou: Tsinghua University; Collaborative Innovation Center for Cancer Medicine
Lina Zhao: Tsinghua University; Collaborative Innovation Center for Cancer Medicine
Huili Wang: Tsinghua University
Xueying Wang: Tsinghua University; Collaborative Innovation Center for Cancer Medicine
Lina Xu: Tsinghua University; Collaborative Innovation Center for Cancer Medicine
Xiaohui Liu: Tsinghua University; Collaborative Innovation Center for Cancer Medicine
Dong Wang: Tsinghua University
Bo Li: Sun Yat-sen University
Tak W. Mak: The Campbell Family Institute for Breast Cancer Research, Princess Margaret Hospital
Wenjing Du: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College
Xiaolu Yang: University of Pennsylvania
Peng Jiang: Tsinghua University; Collaborative Innovation Center for Cancer Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract The Warburg effect is a prominent metabolic feature associated with neoplastic diseases; however, the underlying mechanism remains incompletely understood. TAp73, a structural homolog of the tumor suppressor p53, is frequently overexpressed in human tumors, indicating a proliferative advantage that it can confer to tumor cells. Here we show that TAp73 stimulates the expression of phosphofructokinase-1, liver type (PFKL), which catalyzes the committed step in glycolysis. Through this regulation, TAp73 enhances glucose consumption and lactate excretion, promoting the Warburg effect. By activating PFKL, TAp73 also increases ATP production and bolsters anti-oxidant defense. TAp73 deficiency results in a pronounced reduction in tumorigenic potential, which can be rescued by forced PFKL expression. These findings establish TAp73 as a critical regulator of glycolysis and reveal a mechanism by which tumor cells achieve the Warburg effect to enable oncogenic growth.

Date: 2018
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DOI: 10.1038/s41467-018-07127-8

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