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Regulation of Growth Factor Receptors by Glycosphingolipids

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Glycosignals in Cancer: Mechanisms of Malignant Phenotypes

Abstract

Complex glycosphingolipids (GSLs) are ubiquitous components of animal cell plasma membranes, and many have been structurally characterized. GSLs, including gangliosides, are involved in crucial biological processes such as cell growth, differentiation, and motility. Certain GSLs have been identified as tumor-associated antigens in various types of cancer cells. Early studies of inhibitory effects of gangliosides on cell growth led to the discovery that GSLs modulate (inhibit or enhance) the activation of growth factor (GF) receptor-associated tyrosine kinase, which is triggered by the binding between a GF and its specific receptor. GSLs are localized as clusters at unique microdomains of the plasma membrane, termed glycolipid-enriched microdomains, lipid rafts, or glycosynapses. Various GF receptors (GFRs), including epidermal GFR and hepatocyte GFR, are localized in such membrane microdomains. There is increasing evidence that GSLs modulate the activation of GFR kinases in such microdomains, in which other signaling molecules and regulatory molecules such as integrins and tetraspanins are also localized.

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Authors and Affiliations

  1. Division of Biomembrane Research, Pacific Northwest Research Institute, 720 Broadway, Seattle, WA, 98122, USA

    Sen-itiroh Hakomori & Kazuko Handa

  2. Departments of Pathobiology and Global Health, University of Washington, Seattle, WA, 98040, USA

    Sen-itiroh Hakomori

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  1. Sen-itiroh Hakomori
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  2. Kazuko Handa
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Correspondence to Sen-itiroh Hakomori .

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Editors and Affiliations

  1. Biomedical Sciences, Chubu University, Kasugai, Japan

    Koichi Furukawa

  2. Glycobiology Unit, Sanford-Burnham Med Res Inst, La Jolla, California, USA

    Minoru Fukuda

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© 2016 Springer Japan

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Hakomori, Si., Handa, K. (2016). Regulation of Growth Factor Receptors by Glycosphingolipids. In: Furukawa, K., Fukuda, M. (eds) Glycosignals in Cancer: Mechanisms of Malignant Phenotypes . Springer, Tokyo. https://doi.org/10.1007/978-4-431-55939-9_5

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