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GM3 and cancer

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Abstract

Our studies during the early 1970s showed that expression of GM3, the simplest ganglioside and an abundant animal cell membrane component, is reduced during malignant transformation of cells by oncogenic viruses. Levels of mRNA for GM3 synthase were reduced in avian and mammalian cells transformed by oncoprotein “v-Jun”, and overexpression of GM3 synthase in the transformed cells caused reversion from transformed to normal cell-like phenotype. GM3 has a well-documented inhibitory effect on activation of growth factor receptors (GFRs), particularly epidermal GFR (EGFR). De-N-acetyl GM3, which is expressed in some invasive human cancer cells, has an enhancing effect on EGFR activation. The important role of the sialosyl group of GM3 was demonstrated using NEU3, a plasma membrane-associated sialidase that selectively remove sialic acids from gangliosides GM3 and GD1a and is up-regulated in many human cancer cells. GM3 is highly enriched in a type of membrane microdomain termed “glycosynapse”, and forms complexes with co-localized cell signaling molecules, including Src family kinases, certain tetraspanins (e.g., CD9, CD81, CD82), integrins, and GFRs (e.g., fibroblast growth factor receptor and hepatocyte growth factor receptor c-Met). Studies by our group and others indicate that GM3 modulates cell adhesion, growth, and motility by altering molecular organization in glycosynaptic microdomains and the activation levels of co-localized signaling molecules that are involved in cancer pathogenesis.

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Abbreviations

GFR:

Growth factor receptor

EGFR:

Epidermal growth factor receptor

GSL:

Glycosphingolipid

TS:

Tetraspanin

GPI:

Glycosylphosphatidylinositol

GEM:

Glycolipid-enriched microdomain

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Acknowledgments

Our studies described here were supported mainly by National Cancer Institute Outstanding Investigator Grant (OIG) CA42505 and R01 CA80054, and by The Biomembrane Institute. The authors are grateful to Dr. S. Anderson for English editing of the manuscript

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Authors and Affiliations

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

    Sen-Itiroh Hakomori & Kazuko Handa

  2. Department of Pathobiology, University of Washington, Seattle, WA, 98195, USA

    Sen-Itiroh Hakomori

  3. Department of Global Health, University of Washington, Seattle, WA, 98195, USA

    Sen-Itiroh Hakomori

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Correspondence to Sen-Itiroh Hakomori.

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Hakomori, SI., Handa, K. GM3 and cancer. Glycoconj J 32, 1–8 (2015). https://doi.org/10.1007/s10719-014-9572-4

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