Abstract
BackgroundTransglutaminase-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.MethodsHuman 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.ResultsTGase-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.ConclusionTGase-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.
Highlights
Transglutaminase-4 (TGase-4), known as the Prostate Transglutaminase, is an enzyme found to be expressed predominately in the prostate gland
Monoclonal antibodies of human focal adhesion kinase (FAK) and paxillin were from Transduction laboratories and a neutralising monoclonal antibody to β1-integrin was obtained from R&D Systems Europe (Abbingdon, England)
Immunofluorescence staining of TGase-4, FAK, paxilliln and β1-integrin in cells and tissues Frozen sections of prostate tissues and tumour xenografts were cut at a thickness of 6 μm Manipulation of TGase-4 in prostate cancer cells We previously reported, sublines of CA-HPV-10, which expressed highl levels of TGase-4, were transfected with the anti-TGase-4 ribozyme transgene
Summary
Transglutaminase-4 (TGase-4), 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. Known as transglutaminse (TGase-4), is a member of the transglutaminase [EC 2.3.2.13] family. The influence of TGase-4 on cell invasiveness and migration is not an isolated observation in the TGase family. TGases are involved in regulating apoptosis [12], which may be linked to the fact that TGase-2 is a caspase substrate during apoptosis [13] and a substrate of Calpain [14]. Another calcium regulator, psoriasin (S100A7) is a substrate of TGase-2 [15]
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