Prostate Transglutaminase (TGase-4) Induces Epithelial-to-Mesenchymal Transition in Prostate Cancer Cells

Area of Science:

• Oncology
• Cell Biology
• Biochemistry

Background:

• Prostate cancer (PCa) mortality increases significantly once cancer is no longer organ-confined.
• Epithelial-to-mesenchymal transition (EMT) is a key mechanism driving cancer progression.
• Transglutaminase-4 (TGase-4), expressed in the prostate, is implicated in regulating PCa invasiveness.

Purpose of the Study:

• To investigate the role of TGase-4 in regulating EMT in PCa cells.
• To determine if TGase-4 influences PCa cell motility and expression of EMT markers.

Main Methods:

• Utilized a panel of PCa cell lines (CA-HPV-10, PZ-HPV-7, PC-3, DU-145).
• Generated TGase-4 knockout and overexpression cell models.
• Assessed E-cadherin, N-cadherin, and vimentin expression via immunofluorescence.
• Evaluated cell motility using scratch wound and electric cell-substrate impedance sensing (ECIS) assays.

Main Results:

• Recombinant human TGase-4 (rhTGase-4) significantly increased cell migration and induced loss of E-cadherin with concomitant N-cadherin acquisition.
• Elimination of TGase-4 in CA-HPV-10 cells significantly decreased cell motility and N-cadherin expression.
• TGase-4 treatment altered E-cadherin localization, diminishing intercellular staining.

Conclusions:

• TGase-4 drives EMT in prostate cancer cells by promoting E-cadherin loss, N-cadherin gain, and increased cell migration.
• TGase-4 acts as a key regulator of EMT in prostate epithelia-derived cancer cells.
• TGase-4 is a potential biomarker for prostate cancer disease progression.