Glypican-3 induces oncogenicity by preventing IGF-1R degradation, a process that can be blocked by Grb10

Wei Cheng, Po Chun Huang, Hsiao Mei Chao, Yung Ming Jeng, Hey Chi Hsu, Hung Wei Pan, Wuh Liang Hwu, Yu May Lee

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 promote the growth of IGF-1R negative R- cells. Grb10 overexpression decreased GPC3-promoted cell growth. Therefore, the present study elucidates the mechanisms of GPC3-induced oncogenicity, which may highlight new strategies for the treatment of HCC.

Original languageEnglish
Pages (from-to)80429-80442
Number of pages14
JournalOncotarget
Volume8
Issue number46
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Glypicans
IGF Type 1 Receptor
Hepatocellular Carcinoma
Ubiquitination
Growth
Insulin-Like Growth Factor I
Proto-Oncogene Proteins c-myc
Neoplasms
Serum-Free Culture Media
Phosphorylation
Ligands

Keywords

  • Glypican-3
  • Growth factor receptor-bound protein 10
  • Hepatocellular carcinoma
  • Insulin-like growth factor 1 receptor
  • Ubiquitination

ASJC Scopus subject areas

  • Oncology

Cite this

Glypican-3 induces oncogenicity by preventing IGF-1R degradation, a process that can be blocked by Grb10. / Cheng, Wei; Huang, Po Chun; Chao, Hsiao Mei; Jeng, Yung Ming; Hsu, Hey Chi; Pan, Hung Wei; Hwu, Wuh Liang; Lee, Yu May.

In: Oncotarget, Vol. 8, No. 46, 01.01.2017, p. 80429-80442.

Research output: Contribution to journalArticle

Cheng, Wei ; Huang, Po Chun ; Chao, Hsiao Mei ; Jeng, Yung Ming ; Hsu, Hey Chi ; Pan, Hung Wei ; Hwu, Wuh Liang ; Lee, Yu May. / Glypican-3 induces oncogenicity by preventing IGF-1R degradation, a process that can be blocked by Grb10. In: Oncotarget. 2017 ; Vol. 8, No. 46. pp. 80429-80442.
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