Sonic hedgehog stimulates glycolysis and proliferation of breast cancer cells: Modulation of PFKFB3 activation

Ge, Xin; Lyu, Pengwei; Gu, Yuanting; Li, Lin; Li, Jingruo; Wang, Yan; Zhang, Linfeng; Fu, Chao; Cao, Zhang

doi:10.1016/J.BBRC.2015.07.052

Title: Sonic hedgehog stimulates glycolysis and proliferation of breast cancer cells: Modulation of PFKFB3 activation

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Abstract

Sonic hesgehog (Shh) signaling has been reported to play an essential role in cancer progression. The mechanism of Shh involved in breast cancer carcinogenesis remains unclear. The present study sought to explore whether Shh signaling could regulate the glycolytic metabolism in breast cancers. Overexpression of the smoothed (Smo) and Gli-1 was found in human primary breast cancers. The expressions of Shh and Gli-1 correlated significantly with tumor size and tumor stage. In vitro, human recombinant Shh (rShh) triggered Smo and Gli-1 expression, promoted glucose utilization and lactate production, and accelerated cell proliferation in MCF-7 and MDA-MB-231 cells. Notably, rShh did not alter 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) expression but augmented PFKFB3 phosphorylation on ser{sup 461}, along with elevated fructose-2,6-bisphosphate (F2,6BP) generation by MCF-7 and MDA-MB-231 cells. This effect could be dampened by Smo siRNA but not by Gli-1 siRNA. In addition, our data showed the upregulated expressions of MAPK by rShh and elevatory PFKFB3 phosphorylation by p38/MAPK activated kinase (MK2). In conclusion, our study characterized a novel role of Shh in promoting glycolysis and proliferation of breast cancer cells via PFKFB3 phosphorylation, which was mediated by Smo and p38/MK2. - Highlights: • Overexpression of Smo and Gli-1 was found in human primary breastmore »« less

Authors:

Ge, Xin; Lyu, Pengwei; Gu, Yuanting; Li, Lin; Li, Jingruo; Wang, Yan; Zhang, Linfeng ^[1]; Fu, Chao ^[2]; Cao, Zhang ^[1]

Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China)
Department of Ultrasonography, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China)

Publication Date:: Fri Aug 28 00:00:00 EDT 2015

OSTI Identifier:: 22462228

Resource Type:: Journal Article

Journal Name:: Biochemical and Biophysical Research Communications

Additional Journal Information:: Journal Volume: 464; Journal Issue: 3; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X

Country of Publication:: United States

Language:: English

Subject:: 60 APPLIED LIFE SCIENCES; CARCINOGENESIS; CELL PROLIFERATION; FRUCTOSE; GLUCOSE; GLYCOLYSIS; HUMAN POPULATIONS; IN VITRO; LACTATES; MAMMARY GLANDS; MODULATION; NEOPLASMS; PHOSPHORYLATION; SIGNALS

Citation Formats


                    Ge, Xin, Lyu, Pengwei, Gu, Yuanting, Li, Lin, Li, Jingruo, Wang, Yan, Zhang, Linfeng, Fu, Chao, and Cao, Zhang. Sonic hedgehog stimulates glycolysis and proliferation of breast cancer cells: Modulation of PFKFB3 activation.  United States: N. p., 2015. 
        Web.  doi:10.1016/J.BBRC.2015.07.052.

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                    Ge, Xin, Lyu, Pengwei, Gu, Yuanting, Li, Lin, Li, Jingruo, Wang, Yan, Zhang, Linfeng, Fu, Chao, & Cao, Zhang. Sonic hedgehog stimulates glycolysis and proliferation of breast cancer cells: Modulation of PFKFB3 activation.  United States.  https://doi.org/10.1016/J.BBRC.2015.07.052

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                    Ge, Xin, Lyu, Pengwei, Gu, Yuanting, Li, Lin, Li, Jingruo, Wang, Yan, Zhang, Linfeng, Fu, Chao, and Cao, Zhang. 2015.  
        "Sonic hedgehog stimulates glycolysis and proliferation of breast cancer cells: Modulation of PFKFB3 activation".  United States.  https://doi.org/10.1016/J.BBRC.2015.07.052.

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@article{osti_22462228,

  title        = {Sonic hedgehog stimulates glycolysis and proliferation of breast cancer cells: Modulation of PFKFB3 activation},

  author       = {Ge, Xin and Lyu, Pengwei and Gu, Yuanting and Li, Lin and Li, Jingruo and Wang, Yan and Zhang, Linfeng and Fu, Chao and Cao, Zhang},

  abstractNote = {Sonic hesgehog (Shh) signaling has been reported to play an essential role in cancer progression. The mechanism of Shh involved in breast cancer carcinogenesis remains unclear. The present study sought to explore whether Shh signaling could regulate the glycolytic metabolism in breast cancers. Overexpression of the smoothed (Smo) and Gli-1 was found in human primary breast cancers. The expressions of Shh and Gli-1 correlated significantly with tumor size and tumor stage. In vitro, human recombinant Shh (rShh) triggered Smo and Gli-1 expression, promoted glucose utilization and lactate production, and accelerated cell proliferation in MCF-7 and MDA-MB-231 cells. Notably, rShh did not alter 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) expression but augmented PFKFB3 phosphorylation on ser{sup 461}, along with elevated fructose-2,6-bisphosphate (F2,6BP) generation by MCF-7 and MDA-MB-231 cells. This effect could be dampened by Smo siRNA but not by Gli-1 siRNA. In addition, our data showed the upregulated expressions of MAPK by rShh and elevatory PFKFB3 phosphorylation by p38/MAPK activated kinase (MK2). In conclusion, our study characterized a novel role of Shh in promoting glycolysis and proliferation of breast cancer cells via PFKFB3 phosphorylation, which was mediated by Smo and p38/MK2. - Highlights: • Overexpression of Smo and Gli-1 was found in human primary breast cancers. • Shh promoted glucose utilization, lactate production, and cell proliferation. • Shh did not alter PFKFB3 expression but augmented PFKFB3 phosphorylation on ser461. • Shh acts on PFKFB3 phosphorylation via Smo and p38 MAPK/MK2.},

  doi          = {10.1016/J.BBRC.2015.07.052},

  url          = {https://www.osti.gov/biblio/22462228},
  journal      = {Biochemical and Biophysical Research Communications},

  issn         = {0006-291X},

  number       = 3,

  volume       = 464,

  place        = {United States},

  year         = {Fri Aug 28 00:00:00 EDT 2015},

  month        = {Fri Aug 28 00:00:00 EDT 2015}

}

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