c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3 | Zendy

Huanhuan Ma | Zendy; Jia Zhang | Zendy; Lin Zhou | Zendy; Shixiong Wen | Zendy; Hsiang-Yu Tang | Zendy; Bin Jiang | Zendy; Fengqiong Zhang | Zendy; Muhammad Suleman | Zendy; Dachao Sun | Zendy; Ai Chen | Zendy; Wentao Zhao | Zendy; Furong Lin | Zendy; Ming-Tong Tsau | Zendy; Lu-Min Shih | Zendy; Changchuan Xie | Zendy; Xiaotong Li | Zendy; Donghai Lin | Zendy; LiMan Hung | Zendy; MeiLing Cheng | Zendy; Qinxi Li | Zendy

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c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3

Author(s) -

Huanhuan Ma,

Jia Zhang,

Lin Zhou,

Shixiong Wen,

Hsiang-Yu Tang,

Bin Jiang,

Fengqiong Zhang,

Muhammad Suleman,

Dachao Sun,

Ai Chen,

Wentao Zhao,

Furong Lin,

Ming-Tong Tsau,

Lu-Min Shih,

Changchuan Xie,

Xiaotong Li,

Donghai Lin,

LiMan Hung,

MeiLing Cheng,

Qinxi Li

Publication year - 2020

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2020.03.005

Subject(s) - pentose phosphate pathway , glycolysis , carcinogenesis , microbiology and biotechnology , cancer research , proto oncogene tyrosine protein kinase src , phosphorylation , oxidative phosphorylation , tumor progression , biology , cancer cell , cancer , chemistry , biochemistry , metabolism , genetics

Reprogramming of glucose metabolism is a key event in tumorigenesis and progression. Here, we show that active c-Src stimulates glycolysis by phosphorylating (Tyr194) and activating PFKFB3, a key enzyme that boosts glycolysis by producing fructose-2,6-bisphosphate and activating PFK1. Increased glycolysis intermediates replenish non-oxidative pentose phosphate pathway (PPP) and serine pathway for biosynthesis of cancer cells. PFKFB3 knockout (KO) cells and their counterpart reconstituted with PFKFB3-Y194F show comparably impaired abilities for proliferation, migration, and xenograft formation. Furthermore, PFKFB3-Y194F knockin mice show impaired glycolysis and, mating of these mice with APC min/+ mice attenuates spontaneous colon cancer formation in APC min/+ mice. In summary, we identify a specific mechanism by which c-Src mediates glucose metabolism to meet cancer cells' requirements for maximal biosynthesis and proliferation. The PFKFB3-Tyr194 phosphorylation level highly correlates with c-Src activity in clinical tumor samples, indicating its potential as an evaluation for tumor prognosis.

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