Glypican-3 induces oncogenicity by preventing IGF-1R degradation, a process that can be blocked by Grb10
| Autor: | Yu May Lee, Yung-Ming Jeng, Wuh-Liang Hwu, Hung Wei Pan, Po Chun Huang, Wei Cheng, Hey Chi Hsu, Hsiao Mei Chao |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Gerontology medicine.medical_specialty Oncogenicity ubiquitination Glypican 3 03 medical and health sciences 0302 clinical medicine Internal medicine medicine General hospital biology business.industry GRB10 hepatocellular carcinoma University hospital glypican-3 030104 developmental biology insulin-like growth factor 1 receptor 030220 oncology & carcinogenesis Cancer cell biology.protein Christian ministry business growth factor receptor-bound protein 10 Research Paper Biomedical sciences |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.19035 |
| Popis: | // Wei Cheng 1, 2, 3 , Po-Chun Huang 4, 5 , Hsiao-Mei Chao 6 , Yung-Ming Jeng 7 , Hey-Chi Hsu 7 , Hung-Wei Pan 8 , Wuh-Liang Hwu 9 and Yu-May Lee 4, 5, 9 1 Department of Pathology, Kee-Lung Hospital, Ministry of Health and Welfare, Kee-Lung, Taiwan 2 Ching Kuo Institute of Management and Health, Kee-Lung, Taiwan 3 National Taipei University of Nursing and Health Sciences, Taipei, Taiwan 4 Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan 5 Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan 6 Department of Pathology, Wang Fang Hospital, Taipei Medical University, Taipei, Taiwan 7 Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan 8 Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 9 Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan Correspondence to: Yu-May Lee, email: YML6120@gate.sinica.edu.tw Keywords: glypican-3, hepatocellular carcinoma, insulin-like growth factor 1 receptor, ubiquitination, growth factor receptor-bound protein 10 Received: February 17, 2017 Accepted: June 18, 2017 Published: July 06, 2017 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. |
| Databáze: | OpenAIRE |
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