biostudies-literatureUnknown8(46)Cheng WHepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a major cause of cancer-related death worldwide. Previously, we demonstrated that glypican-3 (GPC3) is highly expressed in HCC, and that GPC3 induces oncogenicity and promotes the growth of cancer cells through IGF-1 receptor (IGF-1R). In the present study, we investigated the mechanisms of GPC3-mediated enhancement of IGF-1R signaling. We demonstrated that GPC3 decreased IGF-1-induced IGF-1R ubiquitination and degradation and increased c-Myc protein levels. GPC3 bound to Grb10, a mediator of ligand-induced receptor ubiquitination, and the overexpression of Grb10 blocked GPC3-enhanced IGF-1-induced ERK phosphorylation. GPC3 promoted the growth of NIH3T3 and PLC-PRF-5 cells in serum-free medium but did not proOncotarget80429-80442https://www.ebi.ac.uk/biostudies/studies/S-EPMC5655209biostudies-literatureGlypican-3 induces oncogenicity by preventing IGF-1R degradation, a process that can be blocked by Grb10.PMC5655209Hwu WLChao HMJeng YMHsu HCLee YMHuang PCCheng WPan HWfalseGlypican-3 induces oncogenicity by preventing IGF-1R degradation, a process that can be blocked by Grb10.Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a major cause of cancer-related death worldwide. Previously, we demonstrated that glypican-3 (GPC3) is highly expressed in HCC, and that GPC3 induces oncogenicity and promotes the growth of cancer cells through IGF-1 receptor (IGF-1R). In the present study, we investigated the mechanisms of GPC3-mediated enhancement of IGF-1R signaling. We demonstrated that GPC3 decreased IGF-1-induced IGF-1R ubiquitination and degradation and increased c-Myc protein levels. GPC3 bound to Grb10, a mediator of ligand-induced receptor ubiquitination, and the overexpression of Grb10 blocked GPC3-enhanced IGF-1-induced ERK phosphorylation. GPC3 promoted the growth of NIH3T3 and PLC-PRF-5 cells in serum-free medium but did not pro2017-01-01T00:00:00Z2017 Oct2025-04-20T00:21:14.602Z2019-03-27T02:59:48ZS-EPMC56552092911331410.18632/oncotarget.19035