Prostate transglutaminase (TGase-4, TGaseP) enhances the adhesion of prostate cancer cells to extracellular matrix, the
- PDF / 1,932,795 Bytes
- 12 Pages / 595.28 x 793.7 pts Page_size
- 50 Downloads / 212 Views
RESEARCH
Open Access
Prostate transglutaminase (TGase-4, TGaseP) enhances the adhesion of prostate cancer cells to extracellular matrix, the potential role of TGase-core domain Wen G Jiang1*, Lin Ye1, Andrew J Sanders1, Fiona Ruge1, Howard G Kynaston1, Richard J Ablin2 and Malcolm D Mason1
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
Background Prostate transglutaminase, also known as transglutaminse4 (TGase-4), is a member of the transglutaminase [EC 2.3.2.13] family. Similar to some of the members, such as keratinocyte TGase, TGase-4 has a relatively restricted pattern of distribution in the body, namely, confined to the prostate gland [1-3]. The role of TGase-4 is not entire clear. Although early studies, mostly using a single technique, have shown that TGase-4 may be reduced in prostate * Correspondence: [email protected] 1 Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK Full list of author information is available at the end of the article
cancer, in comparison with normal prostate tissues [4,5], recent studies have indicated otherwise. Most interestingly, we and others have recently shown that levels of TGase-4 in prostate cancer cells may be linked to the aggressiveness of the cells. For example, overexpression of TGase-4 in prostate cancer cells increases the
Data Loading...
