Type II transglutaminase stimulates epidermal cancer stem cell epithelial-mesenchymal transition

Type II transglutaminase (TG2) is a multifunctional protein that has recently been implicated as having a role in ECS cell survival. In the present study we investigate the role of TG2 in regulating epithelial mesenchymal transition (EMT) in ECS cells. Our studies show that TG2 knockdown or treatmen...

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Main Authors:	Fisher, Matthew L., Adhikary, Gautam, Xu, Wen, Kerr, Candace, Keillor, Jeffrey W., Eckert, Richard L.
Format:	Online
Language:	English
Published:	Impact Journals LLC 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653023/

id	pubmed-4653023
recordtype	oai_dc
spelling	pubmed-46530232015-12-02 Type II transglutaminase stimulates epidermal cancer stem cell epithelial-mesenchymal transition Fisher, Matthew L. Adhikary, Gautam Xu, Wen Kerr, Candace Keillor, Jeffrey W. Eckert, Richard L. Research Paper Type II transglutaminase (TG2) is a multifunctional protein that has recently been implicated as having a role in ECS cell survival. In the present study we investigate the role of TG2 in regulating epithelial mesenchymal transition (EMT) in ECS cells. Our studies show that TG2 knockdown or treatment with TG2 inhibitor, results in a reduced EMT marker expression, and reduced cell migration and invasion. TG2 has several activities, but the most prominent are its transamidase and GTP binding activity. Analysis of a series of TG2 mutants reveals that TG2 GTP binding activity, but not the transamidase activity, is required for expression of EMT markers (Twist, Snail, Slug, vimentin, fibronectin, N-cadherin and HIF-1α), and increased ECS cell invasion and migration. This coupled with reduced expression of E-cadherin. Additional studies indicate that NF&#ξ03BA;B signaling, which has been implicated as mediating TG2 impact on EMT in breast cancer cells, is not involved in TG2 regulation of EMT in skin cancer. These studies suggest that TG2 is required for maintenance of ECS cell EMT, invasion and migration, and suggests that inhibiting TG2 GTP binding/G-protein related activity may reduce skin cancer tumor survival. Impact Journals LLC 2015-05-08 /pmc/articles/PMC4653023/ /pubmed/25971211 Text en Copyright: © 2015 Fisher et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Fisher, Matthew L. Adhikary, Gautam Xu, Wen Kerr, Candace Keillor, Jeffrey W. Eckert, Richard L.
spellingShingle	Fisher, Matthew L. Adhikary, Gautam Xu, Wen Kerr, Candace Keillor, Jeffrey W. Eckert, Richard L. Type II transglutaminase stimulates epidermal cancer stem cell epithelial-mesenchymal transition
author_facet	Fisher, Matthew L. Adhikary, Gautam Xu, Wen Kerr, Candace Keillor, Jeffrey W. Eckert, Richard L.
author_sort	Fisher, Matthew L.
title	Type II transglutaminase stimulates epidermal cancer stem cell epithelial-mesenchymal transition
title_short	Type II transglutaminase stimulates epidermal cancer stem cell epithelial-mesenchymal transition
title_full	Type II transglutaminase stimulates epidermal cancer stem cell epithelial-mesenchymal transition
title_fullStr	Type II transglutaminase stimulates epidermal cancer stem cell epithelial-mesenchymal transition
title_full_unstemmed	Type II transglutaminase stimulates epidermal cancer stem cell epithelial-mesenchymal transition
title_sort	type ii transglutaminase stimulates epidermal cancer stem cell epithelial-mesenchymal transition
description	Type II transglutaminase (TG2) is a multifunctional protein that has recently been implicated as having a role in ECS cell survival. In the present study we investigate the role of TG2 in regulating epithelial mesenchymal transition (EMT) in ECS cells. Our studies show that TG2 knockdown or treatment with TG2 inhibitor, results in a reduced EMT marker expression, and reduced cell migration and invasion. TG2 has several activities, but the most prominent are its transamidase and GTP binding activity. Analysis of a series of TG2 mutants reveals that TG2 GTP binding activity, but not the transamidase activity, is required for expression of EMT markers (Twist, Snail, Slug, vimentin, fibronectin, N-cadherin and HIF-1α), and increased ECS cell invasion and migration. This coupled with reduced expression of E-cadherin. Additional studies indicate that NF&#ξ03BA;B signaling, which has been implicated as mediating TG2 impact on EMT in breast cancer cells, is not involved in TG2 regulation of EMT in skin cancer. These studies suggest that TG2 is required for maintenance of ECS cell EMT, invasion and migration, and suggests that inhibiting TG2 GTP binding/G-protein related activity may reduce skin cancer tumor survival.
publisher	Impact Journals LLC
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653023/
_version_	1613503963886256128

Type II transglutaminase stimulates epidermal cancer stem cell epithelial-mesenchymal transition

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