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Ganglioside GM3 promotes HGF-stimulated motility of murine hepatoma cell through enhanced phosphorylation of cMet at specific tyrosine sites and PI3K/Akt-mediated migration signaling

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Abstract

Ganglioside GM3 plays a well-documented and important role in the regulation of tumor cell proliferation, invasion, and metastasis by modulating tyrosine kinase growth factor receptors. However, the effect of GM3 on the hepatocyte growth factor receptor (HGFR, cMet) has not been fully delineated. In the current study, we investigated how GM3 affects cMet signaling and HGF-stimulated cell motility and migration using three hepatic cancer cell lines of mouse (Hca/A2, Hca/16A3, and Hepa1-6). Decreasing GM3 expression with the use of P4, a specific inhibitor for ganglioside synthesis inhibited the HGF-stimulated phosphorylation of cMet and activity of PI3K/Akt signaling pathway. In contrast, the increased expression of GM3 as a result of adding exogenous GM3 enhanced the HGF-stimulated phosphorylation of cMet and activity of PI3K/Akt signaling pathway. Furthermore, HGF-stimulated cell motility and migration in vitro were inhibited by reduced expression of GM3 and enhanced by increased expression of GM3. All the observations indicate that ganglioside GM3 promotes HGF-stimulated motility of murine hepatoma cell through enhanced phosphorylation of cMet at specific tyrosine sites and PI3K/Akt-mediated migration signaling.

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Abbreviations

P4:

d-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol

GM3:

Neu5Acα2,3Galβ1,4Glcβ1,1Cer

PI3K:

Phosphoinositol-3-kinase

HPTLC:

High-performance thin-layer chromatography

MAPK:

Mitogen-activated protein kinase

GSK:

Glycogen synthase kinase-3

PLCγ1:

Phospholipaseγ1

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Acknowledgments

This study was supported by a Grant from the National Program on Key Basic Research Project (973 Program) (No. 2012CB822103) and Grant 2009T022 from Liaoning Province Education Bureau.

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Authors and Affiliations

  1. Department of Clinical Laboratory, Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China

    Ying Li

  2. Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, 116044, China

    Xiaohua Huang, Jianing Zhang & Keli Ma

  3. Department of Clinical Biochemistry, College of Laboratory Medicine, Dalian Medical University, Dalian, 116044, China

    Xiaohua Huang

  4. Department of Orthopaedics, First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian, 116011, China

    Weiliang Zhong

Authors
  1. Ying Li
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  2. Xiaohua Huang
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  3. Weiliang Zhong
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  4. Jianing Zhang
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  5. Keli Ma
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Corresponding author

Correspondence to Keli Ma.

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Ying Li and Xiaohua Huang contributed equally to this study.

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Li, Y., Huang, X., Zhong, W. et al. Ganglioside GM3 promotes HGF-stimulated motility of murine hepatoma cell through enhanced phosphorylation of cMet at specific tyrosine sites and PI3K/Akt-mediated migration signaling. Mol Cell Biochem 382, 83–92 (2013). https://doi.org/10.1007/s11010-013-1720-9

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  • DOI: https://doi.org/10.1007/s11010-013-1720-9

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