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Transglutaminase 2 Promotes Migration and Invasion of Lung Cancer Cells

Lung cancer is the leading cause of cancer deaths worldwide. Given that the major threat of cancer is metastasis, delineation of the molecular mechanism underlying it would help devise therapeutic strategies. Transglutaminase 2 (TG2), belonging to the transglutaminase superfamily, is a versatile pro...

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Autores principales: Lee, Hung-Tsung, Huang, Cheng-Hsieh, Chen, Wuan-Chun, Tsai, Chi-Shan, Chao, Yu-Lin, Liu, Szu-Han, Chen, Jun-Hong, Wu, Yi-Ying, Lee, Yi-Ju
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cognizant Communication Corporation 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844758/
https://www.ncbi.nlm.nih.gov/pubmed/29301592
http://dx.doi.org/10.3727/096504018X15149761920868
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author Lee, Hung-Tsung
Huang, Cheng-Hsieh
Chen, Wuan-Chun
Tsai, Chi-Shan
Chao, Yu-Lin
Liu, Szu-Han
Chen, Jun-Hong
Wu, Yi-Ying
Lee, Yi-Ju
author_facet Lee, Hung-Tsung
Huang, Cheng-Hsieh
Chen, Wuan-Chun
Tsai, Chi-Shan
Chao, Yu-Lin
Liu, Szu-Han
Chen, Jun-Hong
Wu, Yi-Ying
Lee, Yi-Ju
author_sort Lee, Hung-Tsung
collection PubMed
description Lung cancer is the leading cause of cancer deaths worldwide. Given that the major threat of cancer is metastasis, delineation of the molecular mechanism underlying it would help devise therapeutic strategies. Transglutaminase 2 (TG2), belonging to the transglutaminase superfamily, is a versatile protein with enzymatic and nonenzymatic functions. It mainly localizes inside the cell, but also appears extracellularly. Recent findings have demonstrated the involvement of TG2 in cancer development. Here we examine the role of TG2 in metastasis of lung cancer using a lung cancer cell line CL1-0, which exhibits low invasiveness, and its invasive subline CL1-5. Our results show that CL1-5 cells express a higher amount of TG2 than CL1-0 cells. Overexpression of TG2 in CL1-0 enhances cell migration and invasion, and lowering TG2 expression in CL1-5 cells reduces their ability to do so. The transamidase activity of TG2 is not required since cells expressing the inactive TG2 mutant or treated with a TG2 inhibitor are still able to migrate and invade. TG2-stimulated migration and invasion are, at least in part, mediated by Rac, as inhibition of Rac activity suppresses cell migration and invasion. Lastly, exogenous application of recombinant TG2 protein to CL1-0 cells substantially augments cell migration and invasion, suggesting the significance of extracellular TG2 in promoting these events. Collectively, our results show that TG2 plays a positive role in cell migration and invasion, and this might help metastasis of lung cancer cells.
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spelling pubmed-78447582021-02-16 Transglutaminase 2 Promotes Migration and Invasion of Lung Cancer Cells Lee, Hung-Tsung Huang, Cheng-Hsieh Chen, Wuan-Chun Tsai, Chi-Shan Chao, Yu-Lin Liu, Szu-Han Chen, Jun-Hong Wu, Yi-Ying Lee, Yi-Ju Oncol Res Article Lung cancer is the leading cause of cancer deaths worldwide. Given that the major threat of cancer is metastasis, delineation of the molecular mechanism underlying it would help devise therapeutic strategies. Transglutaminase 2 (TG2), belonging to the transglutaminase superfamily, is a versatile protein with enzymatic and nonenzymatic functions. It mainly localizes inside the cell, but also appears extracellularly. Recent findings have demonstrated the involvement of TG2 in cancer development. Here we examine the role of TG2 in metastasis of lung cancer using a lung cancer cell line CL1-0, which exhibits low invasiveness, and its invasive subline CL1-5. Our results show that CL1-5 cells express a higher amount of TG2 than CL1-0 cells. Overexpression of TG2 in CL1-0 enhances cell migration and invasion, and lowering TG2 expression in CL1-5 cells reduces their ability to do so. The transamidase activity of TG2 is not required since cells expressing the inactive TG2 mutant or treated with a TG2 inhibitor are still able to migrate and invade. TG2-stimulated migration and invasion are, at least in part, mediated by Rac, as inhibition of Rac activity suppresses cell migration and invasion. Lastly, exogenous application of recombinant TG2 protein to CL1-0 cells substantially augments cell migration and invasion, suggesting the significance of extracellular TG2 in promoting these events. Collectively, our results show that TG2 plays a positive role in cell migration and invasion, and this might help metastasis of lung cancer cells. Cognizant Communication Corporation 2018-09-14 /pmc/articles/PMC7844758/ /pubmed/29301592 http://dx.doi.org/10.3727/096504018X15149761920868 Text en Copyright © 2018 Cognizant, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This article is licensed under a Creative Commons Attribution-NonCommercial NoDerivatives 4.0 International License.
spellingShingle Article
Lee, Hung-Tsung
Huang, Cheng-Hsieh
Chen, Wuan-Chun
Tsai, Chi-Shan
Chao, Yu-Lin
Liu, Szu-Han
Chen, Jun-Hong
Wu, Yi-Ying
Lee, Yi-Ju
Transglutaminase 2 Promotes Migration and Invasion of Lung Cancer Cells
title Transglutaminase 2 Promotes Migration and Invasion of Lung Cancer Cells
title_full Transglutaminase 2 Promotes Migration and Invasion of Lung Cancer Cells
title_fullStr Transglutaminase 2 Promotes Migration and Invasion of Lung Cancer Cells
title_full_unstemmed Transglutaminase 2 Promotes Migration and Invasion of Lung Cancer Cells
title_short Transglutaminase 2 Promotes Migration and Invasion of Lung Cancer Cells
title_sort transglutaminase 2 promotes migration and invasion of lung cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844758/
https://www.ncbi.nlm.nih.gov/pubmed/29301592
http://dx.doi.org/10.3727/096504018X15149761920868
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