Prostate transglutaminase (TGase-4) induces epithelial-to-mesenchymal transition in prostate cancer cells

Ablin, Richard J, Owen, Sioned and Jiang, Wen ORCID: https://orcid.org/0000-0002-3283-1111 2017. Prostate transglutaminase (TGase-4) induces epithelial-to-mesenchymal transition in prostate cancer cells. Anticancer Research 37 (2) , pp. 481-488. 10.21873/anticanres.11340

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Abstract

More men die with prostate cancer (PCa) than from it. However, once PCa is no longer organ-confined, it is associated with significant mortality. Epithelial-to-mesenchymal transition (EMT) is one mechanism facilitating progression in cancer. Our studies of transglutaminase-4 TGase-4, a member of the TGase family, expressed in the prostate gland, have implicated it in the regulation of the invasive properties of PCa. The present study investigated the role of TGase-4 on EMT of PCa cells. Materials and Methods: A panel of PCa cell lines: CA-HPV-10, PZ-HPV-7, PC-3 and DU-145 were used. An anti- TGase-4 transgene was constructed to eliminate the expression of TGase-4 in CA-HPV-10 (positive for TGase-4). An expression construct for human TGase-4 was used to transfect PCa cells negative for TGase-4. The pattern of E-cadherin, N-cadherin and vimentin in these cells were evaluated using immunofluorescent staining. Cell motility was assessed using scratch wounding and ekectric cell-substrate impedance sensing (ECIS) assays. Results: Treatment of PZ-HPV-7 and CA-HPV- 10 cells with rhTGase-4 resulted in a significant increase in cell migration (1,407.9 Ω±6.4 Ω vs. 1,691.2 Ω±8.3 Ω in non-treated and rhTGase-4 treated cells, respectively, p<0.01). Cells strongly expressing E-cadherin showed substantial changes of E-cadherin staining in that, after treatment with TGase-4, the intercellular staining of E-cadherin was diminished. Concomitantly, there was acquisition of N-cadherin in TGase- 4-treated cells. Elimination of TGase-4 from CA-HPV-10 cells significantly decreased cell motility (128.1 Ω±107.4 Ω vs. 31.7 Ω±26.2 Ω, in CA-HPV-10 control and CA-HPV-10/TGase-4 knockout cells). Knocking- out TGase-4 from CA-HPV-10 cells also resulted in substantial loss of N-cadherin in the cells. Conclusion: TGase-4 resulted in loss of E-cadherin/acquisition of N-cadherin and cell migration indicating it is a keen regulator of EMT in prostate epithelia-derived cancer cells. In concert with its other properties involved in disease progression, the present observations suggest TGase-4 as a prospective marker of disease progression.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	Prostate transglutaminase, prostate cancer, EMT, epithelial–mesenchymal transition, cell migration, cadherin switch.
Publisher:	International Institute of Anticancer Research
ISSN:	0250-7005
Funders:	Cancer Research Wales, Robert Benjamin Ablin Foundation for Cancer Research, Albert Hung Foundation, the Life Sciences National Research Network Wales (LSRNW/Ser Cymru).
Related URLs:	http://ar.iiarjournals.org/content/37/2....
Date of First Compliant Deposit:	9 February 2017
Date of Acceptance:	12 January 2017
Last Modified:	03 May 2023 11:20
URI:	https://orca.cardiff.ac.uk/id/eprint/98176

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