c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3

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; Li Man Hung; Mei Ling Cheng; Qinxi Li

doi:10.1016/j.celrep.2020.03.005

c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3

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, Li Man Hung^*, Mei Ling Cheng, Qinxi Li

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

57 Scopus citations

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 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.

Original language	English
Pages (from-to)	4235-4249.e6
Journal	Cell Reports
Volume	30
Issue number	12
DOIs	https://doi.org/10.1016/j.celrep.2020.03.005
State	Published - 24 03 2020

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© 2020 The Author(s)

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Ma, H., Zhang, J., Zhou, L., Wen, S., Tang, H. Y., Jiang, B., Zhang, F., Suleman, M., Sun, D., Chen, A., Zhao, W., Lin, F., Tsau, M. T., Shih, L. M., Xie, C., Li, X., Lin, D., Hung, L. M., Cheng, M. L., & Li, Q. (2020). c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3. Cell Reports, 30(12), 4235-4249.e6. https://doi.org/10.1016/j.celrep.2020.03.005

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title = "c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3",

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{\textquoteright} 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.",

author = "Huanhuan Ma and Jia Zhang and Lin Zhou and Shixiong Wen and Tang, \{Hsiang Yu\} and Bin Jiang and Fengqiong Zhang and Muhammad Suleman and Dachao Sun and Ai Chen and Wentao Zhao and Furong Lin and Tsau, \{Ming Tong\} and Shih, \{Lu Min\} and Changchuan Xie and Xiaotong Li and Donghai Lin and Hung, \{Li Man\} and Cheng, \{Mei Ling\} and Qinxi Li",

note = "Publisher Copyright: {\textcopyright} 2020 The Author(s)",

year = "2020",

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day = "24",

doi = "10.1016/j.celrep.2020.03.005",

language = "英语",

volume = "30",

pages = "4235--4249.e6",

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TY - JOUR

T1 - c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3

AU - Ma, Huanhuan

AU - Zhang, Jia

AU - Zhou, Lin

AU - Wen, Shixiong

AU - Tang, Hsiang Yu

AU - Jiang, Bin

AU - Zhang, Fengqiong

AU - Suleman, Muhammad

AU - Sun, Dachao

AU - Chen, Ai

AU - Zhao, Wentao

AU - Lin, Furong

AU - Tsau, Ming Tong

AU - Shih, Lu Min

AU - Xie, Changchuan

AU - Li, Xiaotong

AU - Lin, Donghai

AU - Hung, Li Man

AU - Cheng, Mei Ling

AU - Li, Qinxi

PY - 2020/3/24

Y1 - 2020/3/24

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85082021451

U2 - 10.1016/j.celrep.2020.03.005

DO - 10.1016/j.celrep.2020.03.005

M3 - 文章

C2 - 32209481

AN - SCOPUS:85082021451

SN - 2211-1247

VL - 30

SP - 4235-4249.e6

JO - Cell Reports

JF - Cell Reports

IS - 12

ER -

c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3

Abstract

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