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Glypican-3-mediated oncogenesis involves the Insulin-like growth factor-signaling pathway

Glypican-3 (gpc3) is the gene responsible for Simpson-Golabi-Behmel overgrowth syndrome. Previously, we have shown that GPC3 is overexpressed in hepatocellular carcinoma (HCC). In this study, we demonstrated the mechanisms for GPC3-mediated oncogenesis. Firstly, GPC3 overexpression in NIH3T3 cells g...

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Autores principales: Cheng, Wei, Tseng, Chia-Jen, Lin, Tom T.C., Cheng, I., Pan, Hung-Wei, Hsu, Hey-Chi, Lee, Yu-May
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2500215/
https://www.ncbi.nlm.nih.gov/pubmed/18413366
http://dx.doi.org/10.1093/carcin/bgn091
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author Cheng, Wei
Tseng, Chia-Jen
Lin, Tom T.C.
Cheng, I.
Pan, Hung-Wei
Hsu, Hey-Chi
Lee, Yu-May
author_facet Cheng, Wei
Tseng, Chia-Jen
Lin, Tom T.C.
Cheng, I.
Pan, Hung-Wei
Hsu, Hey-Chi
Lee, Yu-May
author_sort Cheng, Wei
collection PubMed
description Glypican-3 (gpc3) is the gene responsible for Simpson-Golabi-Behmel overgrowth syndrome. Previously, we have shown that GPC3 is overexpressed in hepatocellular carcinoma (HCC). In this study, we demonstrated the mechanisms for GPC3-mediated oncogenesis. Firstly, GPC3 overexpression in NIH3T3 cells gave to cancer cell phenotypes including growing in serum-free medium and forming colonies in soft agar, or on the other way, GPC3 knockdown in HuH-7 cells decreased oncogenecity. We further demonstrated that GPC3 bound specifically through its N-terminal proline-rich region to both Insulin-like growth factor (IGF)-II and IGF-1R. GPC3 stimulated the phosphorylation of IGF-1R and the downstream signaling molecule extracellular signal-regulated kinase (ERK) in an IGF-II-dependent way. Also, GPC3 knockdown in HCC cells decreased the phosphorylation of both IGF-1R and ERK. Therefore, GPC3 confers oncogenecity through the interaction between IGF-II and its receptor, and the subsequent activation of the IGF-signaling pathway. This data are novel to the current understanding of the role of GPC3 in HCC and will be important in future developments of cancer therapy.
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spelling pubmed-25002152009-02-25 Glypican-3-mediated oncogenesis involves the Insulin-like growth factor-signaling pathway Cheng, Wei Tseng, Chia-Jen Lin, Tom T.C. Cheng, I. Pan, Hung-Wei Hsu, Hey-Chi Lee, Yu-May Carcinogenesis Cancer Biology Glypican-3 (gpc3) is the gene responsible for Simpson-Golabi-Behmel overgrowth syndrome. Previously, we have shown that GPC3 is overexpressed in hepatocellular carcinoma (HCC). In this study, we demonstrated the mechanisms for GPC3-mediated oncogenesis. Firstly, GPC3 overexpression in NIH3T3 cells gave to cancer cell phenotypes including growing in serum-free medium and forming colonies in soft agar, or on the other way, GPC3 knockdown in HuH-7 cells decreased oncogenecity. We further demonstrated that GPC3 bound specifically through its N-terminal proline-rich region to both Insulin-like growth factor (IGF)-II and IGF-1R. GPC3 stimulated the phosphorylation of IGF-1R and the downstream signaling molecule extracellular signal-regulated kinase (ERK) in an IGF-II-dependent way. Also, GPC3 knockdown in HCC cells decreased the phosphorylation of both IGF-1R and ERK. Therefore, GPC3 confers oncogenecity through the interaction between IGF-II and its receptor, and the subsequent activation of the IGF-signaling pathway. This data are novel to the current understanding of the role of GPC3 in HCC and will be important in future developments of cancer therapy. Oxford University Press 2008-07 2008-04-15 /pmc/articles/PMC2500215/ /pubmed/18413366 http://dx.doi.org/10.1093/carcin/bgn091 Text en © The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org
spellingShingle Cancer Biology
Cheng, Wei
Tseng, Chia-Jen
Lin, Tom T.C.
Cheng, I.
Pan, Hung-Wei
Hsu, Hey-Chi
Lee, Yu-May
Glypican-3-mediated oncogenesis involves the Insulin-like growth factor-signaling pathway
title Glypican-3-mediated oncogenesis involves the Insulin-like growth factor-signaling pathway
title_full Glypican-3-mediated oncogenesis involves the Insulin-like growth factor-signaling pathway
title_fullStr Glypican-3-mediated oncogenesis involves the Insulin-like growth factor-signaling pathway
title_full_unstemmed Glypican-3-mediated oncogenesis involves the Insulin-like growth factor-signaling pathway
title_short Glypican-3-mediated oncogenesis involves the Insulin-like growth factor-signaling pathway
title_sort glypican-3-mediated oncogenesis involves the insulin-like growth factor-signaling pathway
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2500215/
https://www.ncbi.nlm.nih.gov/pubmed/18413366
http://dx.doi.org/10.1093/carcin/bgn091
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