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

Malcolm D Mason²  Richard J Ablin¹  Howard G Kynaston²  Fiona Ruge²  Andrew J Sanders²  Lin Ye²  Wen G Jiang² 

[1] Department of Pathology, Health Sciences Center, University of Arizona College of Medicine and the Arizona Cancer Center, 1501 N. Campbell Avenue, P.O. Box 245043, Tucson, AZ AZ 85724-5043, USA;Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK

关键词: Prostate cancer;    Electric cell sensing;    Integrins;    Paxillin;    Focal adhesion kinase;    Cell-matrix adhesion;    Transglutaminase-4;    Transglutaminase;   

Others  :  824878
DOI  :  10.1186/1479-5876-11-269

 received in 2013-04-04, accepted in 2013-10-09,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Jiang et al.; licensee BioMed Central Ltd.

【 图 表 】

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