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

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
    • Publication Information:
      Publication: <2002- >: San Diego, CA : Elsevier
      Original Publication: New York, Academic Press.
    • Subject Terms:
      Glycolysis*; Breast Neoplasms/*metabolism ; Breast Neoplasms/*pathology ; Hedgehog Proteins/*metabolism ; Phosphofructokinase-2/*metabolism; Adult ; Case-Control Studies ; Cell Line, Tumor ; Cell Proliferation ; Enzyme Activation ; Female ; Glucose/metabolism ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Lactates/metabolism ; Middle Aged ; Phosphorylation ; Protein Serine-Threonine Kinases/metabolism ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; Reference Values ; Serine/metabolism ; Smoothened Receptor ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Zinc Finger Protein GLI1 ; p38 Mitogen-Activated Protein Kinases/metabolism
    • 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(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.
      (Copyright © 2015 Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: Breast cancer; Glycolysis; PFKFB3; Proliferation; Sonic hedgehog; p38/MAPK activated kinase
    • Accession Number:
      0 (GLI1 protein, human)
      0 (Hedgehog Proteins)
      0 (Intracellular Signaling Peptides and Proteins)
      0 (Lactates)
      0 (Receptors, G-Protein-Coupled)
      0 (SHH protein, human)
      0 (SMO protein, human)
      0 (Smoothened Receptor)
      0 (Transcription Factors)
      0 (Zinc Finger Protein GLI1)
      452VLY9402 (Serine)
      EC 2.7.1.- (MAP-kinase-activated kinase 2)
      EC 2.7.1.105 (PFKFB3 protein, human)
      EC 2.7.1.105 (Phosphofructokinase-2)
      EC 2.7.11.1 (Protein Serine-Threonine Kinases)
      EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
      IY9XDZ35W2 (Glucose)
    • Publication Date:
      Date Created: 20150715 Date Completed: 20151110 Latest Revision: 20211203
    • Publication Date:
      20250114
    • Accession Number:
      10.1016/j.bbrc.2015.07.052
    • Accession Number:
      26171876