2. Academic Validation
  3. c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3

c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3

  • Cell Rep. 2020 Mar 24;30(12):4235-4249.e6. doi: 10.1016/j.celrep.2020.03.005.
Huanhuan Ma 1,  Jia Zhang 1,  Lin Zhou 1,  Shixiong Wen 1,  Hsiang-Yu Tang 2,  Bin Jiang 1,  Fengqiong Zhang 1,  Muhammad Suleman 1,  Dachao Sun 1,  Ai Chen 1,  Wentao Zhao 1,  Furong Lin 1,  Ming-Tong Tsau 2,  Lu-Min Shih 2,  Changchuan Xie 1,  Xiaotong Li 1,  Donghai Lin 3,  Li-Man Hung 4,  Mei-Ling Cheng 5,  Qinxi Li 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
  • 2 Metabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan City 33302, Taiwan.
  • 3 Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, China.
  • 4 Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 33302, Taiwan; Center for Healthy and Aging Research, Chang Gung University, Taoyuan City 33302, Taiwan; Kidney Research Center, Chang Gung Memorial Hospital, Taoyuan City 33302, Taiwan. Electronic address: lisahung@mail.cgu.edu.tw.
  • 5 Metabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan City 33302, Taiwan; Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 33302, Taiwan; Clinical Metabolomics Core Laboratory, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan. Electronic address: chengm@mail.cgu.edu.tw.
  • 6 State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; Cancer Research Center of Xiamen University, Xiamen, Fujian 361102, China. Electronic address: liqinxi@xmu.edu.cn.
PMID: 32209481 DOI: 10.1016/j.celrep.2020.03.005
Abstract

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 APCmin/+ mice attenuates spontaneous colon Cancer formation in APCmin/+ 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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
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  • HY-13805
    98.34%, Src抑制剂
    Src
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