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Role of glypican-1 in regulating multiple cellular signaling pathways

期刊

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
卷 321, 期 5, 页码 C846-C858

出版社

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00290.2021

关键词

cancer; glypican-1; signaling pathways; therapeutic target

资金

  1. Intramural Research Program of NIH, Center for Cancer Research (CCR) , National Cancer Institute (NCI) [Z01 BC010891, ZIA BC010891]

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Glypican-1 (GPC1) modulates various signaling pathways by interacting with pathway ligands and receptors, impacting the pathways' activation or inhibition based on specific GPC1 domain interactions with pathway components and cell surface context.
Glypican-1 (GPC1) is one of the six glypican family members in humans. It is composed of a core protein with three heparan sulfate chains and attached to the cell membrane by a glycosyl-phosphatidylinositol anchor. GPC1 modulates various signaling pathways including fibroblast growth factors (FGF), vascular endothelial growth factor-A (VEGF-A), transforming growth factor-beta (TGF-beta), Wnt Hedgehog (Hh), and bone morphogenic protein (BMP) through specific interactions with pathway ligands and receptors. The impact of these interactions on signaling pathways, activating or inhibitory, is dependent upon specific GPC1 domain interaction with pathway components, as well as cell surface context. In this review, we summarize the current understanding of the structure of GPC1, as well as its role in regulating multiple signaling pathways. We focus on the functions of GPC1 in cancer cells and how new insights into these signaling processes can inform its translational potential as a therapeutic target in cancer.

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