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Prostate transglutaminase (TGase-4, TGaseP) enhances the adhesion of prostate cancer cells to extracellular matrix, the potential role of TGase-core domain

Jiang, Wen Guo ORCID: https://orcid.org/0000-0002-3283-1111, Ye, Lin ORCID: https://orcid.org/0000-0002-0303-2409, Sanders, Andrew James ORCID: https://orcid.org/0000-0002-7997-5286, Ruge, Fiona, Kynaston, Howard ORCID: https://orcid.org/0000-0003-1902-9930, Ablin, Richard J. and Mason, Malcolm David ORCID: https://orcid.org/0000-0003-1505-2869 2013. Prostate transglutaminase (TGase-4, TGaseP) enhances the adhesion of prostate cancer cells to extracellular matrix, the potential role of TGase-core domain. Journal of Translational Medicine 11 , 269. 10.1186/1479-5876-11-269

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Abstract

Background: Transglutaminase-4 (TGase-4), also known as the Prostate Transglutaminase, is an enzyme found to be expressed predominately in the prostate gland. The protein has been recently reported to influence the migration and invasiveness of prostate cancer cells. The present study aimed to investigate the influence of TGase-4 on cell-matrix adhesion and search for the candidate active domain[s] within the protein. Methods: Human prostate cancer cell lines and prostate tissues were used. Plasmids that encoded different domains and full length of TGase-4 were constructed and used to generate sublines that expressed different domains. The impact of TGase-4 on in vitro cell-matrix adhesion, cell migration, growth and in vivo growth were investigated. Interactions between TGase-4 and focal adhesion complex proteins were investigated using immunoprecipitation, immunofluorescence and phosphospecific antibodies. Results: TGase-4 markedly increased cell-matrix adhesion and cellular migration, and resulted in a rapid growth of prostate tumours in vivo. This effect resided in the Core-domain of the TGase-4 protein. TGase-4 was found to co-precipitate and co-localise with focal adhesion kinase (FAK) and paxillin, in cells, human prostate tissues and tumour xenografts. FAK small inhibitor was able to block the action mediated by TGase-4 and TGase-4 core domain. Conclusion: TGase-4 is an important regulator of cell-matrix adhesion of prostate cancer cells. This effect is predominately mediated by its core domain and requires the participation of focal adhesion complex proteins. Keywords: Transglutaminase, Transglutaminase-4, Cell-matrix adhesion, Focal adhesion kinase, Paxillin, Integrins, Electric cell sensing, Prostate cancer

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Additional Information: © 2013 Jiang et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Publisher: BioMed Central
Date of First Compliant Deposit: 30 March 2016
Last Modified: 05 Dec 2023 02:43
URI: https://orca.cardiff.ac.uk/id/eprint/75826

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