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


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.

SUBMITTER: Li L 

PROVIDER: S-EPMC6224601 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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

Li Le L   Li Lijia L   Li Wei W   Chen Taiqi T   Bin Zou   Zhao Lina L   Wang Huili H   Wang Xueying X   Xu Lina L   Liu Xiaohui X   Wang Dong D   Li Bo B   Mak Tak W TW   Du Wenjing W   Yang Xiaolu X   Jiang Peng P  

Nature communications 20181108 1


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,  ...[more]

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