Identification of the atypical cadherin FAT1 as a novel glypican-3 interacting protein in liver cancer cells

Abstract Glypican-3 (GPC3) is a cell surface heparan sulfate proteoglycan that is being evaluated as an emerging therapeutic target in hepatocellular carcinoma (HCC). GPC3 has been shown to interact with several extracellular signaling molecules, including Wnt, HGF, and Hedgehog. Here, we reported a...

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Autores principales:	Panpan Meng, Yi-Fan Zhang, Wangli Zhang, Xin Chen, Tong Xu, Sheng Hu, Xinjun Liang, Mingqian Feng, Xiaoqing Yang, Mitchell Ho
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/329ef05cc3ff4f34a6454608732c6a4c
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spelling	oai:doaj.org-article:329ef05cc3ff4f34a6454608732c6a4c2021-12-02T15:13:14ZIdentification of the atypical cadherin FAT1 as a novel glypican-3 interacting protein in liver cancer cells10.1038/s41598-020-79524-32045-2322https://doaj.org/article/329ef05cc3ff4f34a6454608732c6a4c2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79524-3https://doaj.org/toc/2045-2322Abstract Glypican-3 (GPC3) is a cell surface heparan sulfate proteoglycan that is being evaluated as an emerging therapeutic target in hepatocellular carcinoma (HCC). GPC3 has been shown to interact with several extracellular signaling molecules, including Wnt, HGF, and Hedgehog. Here, we reported a cell surface transmembrane protein (FAT1) as a new GPC3 interacting protein. The GPC3 binding region on FAT1 was initially mapped to the C-terminal region (Q14517, residues 3662-4181), which covered a putative receptor tyrosine phosphatase (RTP)-like domain, a Laminin G-like domain, and five EGF-like domains. Fine mapping by ELISA and flow cytometry showed that the last four EGF-like domains (residues 4013-4181) contained a specific GPC3 binding site, whereas the RTP domain (residues 3662-3788) and the downstream Laminin G-2nd EGF-like region (residues 3829-4050) had non-specific GPC3 binding. In support of their interaction, GPC3 and FAT1 behaved concomitantly or at a similar pattern, e.g. having elevated expression in HCC cells, being up-regulated under hypoxia conditions, and being able to regulate the expression of EMT-related genes Snail, Vimentin, and E-Cadherin and promoting HCC cell migration. Taken together, our study provides the initial evidence for the novel mechanism of GPC3 and FAT1 in promoting HCC cell migration.Panpan MengYi-Fan ZhangWangli ZhangXin ChenTong XuSheng HuXinjun LiangMingqian FengXiaoqing YangMitchell HoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Panpan Meng Yi-Fan Zhang Wangli Zhang Xin Chen Tong Xu Sheng Hu Xinjun Liang Mingqian Feng Xiaoqing Yang Mitchell Ho Identification of the atypical cadherin FAT1 as a novel glypican-3 interacting protein in liver cancer cells
description	Abstract Glypican-3 (GPC3) is a cell surface heparan sulfate proteoglycan that is being evaluated as an emerging therapeutic target in hepatocellular carcinoma (HCC). GPC3 has been shown to interact with several extracellular signaling molecules, including Wnt, HGF, and Hedgehog. Here, we reported a cell surface transmembrane protein (FAT1) as a new GPC3 interacting protein. The GPC3 binding region on FAT1 was initially mapped to the C-terminal region (Q14517, residues 3662-4181), which covered a putative receptor tyrosine phosphatase (RTP)-like domain, a Laminin G-like domain, and five EGF-like domains. Fine mapping by ELISA and flow cytometry showed that the last four EGF-like domains (residues 4013-4181) contained a specific GPC3 binding site, whereas the RTP domain (residues 3662-3788) and the downstream Laminin G-2nd EGF-like region (residues 3829-4050) had non-specific GPC3 binding. In support of their interaction, GPC3 and FAT1 behaved concomitantly or at a similar pattern, e.g. having elevated expression in HCC cells, being up-regulated under hypoxia conditions, and being able to regulate the expression of EMT-related genes Snail, Vimentin, and E-Cadherin and promoting HCC cell migration. Taken together, our study provides the initial evidence for the novel mechanism of GPC3 and FAT1 in promoting HCC cell migration.
format	article
author	Panpan Meng Yi-Fan Zhang Wangli Zhang Xin Chen Tong Xu Sheng Hu Xinjun Liang Mingqian Feng Xiaoqing Yang Mitchell Ho
author_facet	Panpan Meng Yi-Fan Zhang Wangli Zhang Xin Chen Tong Xu Sheng Hu Xinjun Liang Mingqian Feng Xiaoqing Yang Mitchell Ho
author_sort	Panpan Meng
title	Identification of the atypical cadherin FAT1 as a novel glypican-3 interacting protein in liver cancer cells
title_short	Identification of the atypical cadherin FAT1 as a novel glypican-3 interacting protein in liver cancer cells
title_full	Identification of the atypical cadherin FAT1 as a novel glypican-3 interacting protein in liver cancer cells
title_fullStr	Identification of the atypical cadherin FAT1 as a novel glypican-3 interacting protein in liver cancer cells
title_full_unstemmed	Identification of the atypical cadherin FAT1 as a novel glypican-3 interacting protein in liver cancer cells
title_sort	identification of the atypical cadherin fat1 as a novel glypican-3 interacting protein in liver cancer cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/329ef05cc3ff4f34a6454608732c6a4c
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Identification of the atypical cadherin FAT1 as a novel glypican-3 interacting protein in liver cancer cells

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