CTEN-induced TGF-β1 expression facilitates EMT and enhances paclitaxel resistance in bladder cancer cells

Objectives: To investigate the role of C-terminal tensin-like (CTEN) in mediating chemotherapy resistance via epithelial-mesenchymal transition (EMT) in bladder Cancer (BC) cells, through the regulation of transforming growth factor-β1 (TGF-β1) expression.

Methods: Lentiviral vectors were used to create CTEN overexpression and knockdown constructs, which were then introduced into paclitaxel-resistant BC cell lines. The effects of CTEN manipulation on cell proliferation and drug sensitivity was assessed using the CCK-8 assay, and Apoptosis was evaluated by flow cytometry. The expression levels of CTEN, TGF-β1, and EMT markers were quantified by RT-qPCR and Western blot analysis. The interaction between CTEN and TGF-β1 and its effect on TGF-β1 methylation were studied using bisulfite Sequencing PCR and co-immunoprecipitation.

Results: Overexpression of CTEN in BC cells was associated with decreased paclitaxel efficacy, reduced Apoptosis, and elevated levels of TGF-β1 and EMT-related proteins. CTEN was found to bind TGF-β1, inhibiting its methylation and thereby promoting TGF-β1 upregulation. This increase in TGF-β1 expression facilitated the EMT process and enhanced drug resistance in BC cells.

Conclusions: The induction of TGF-β1 expression by CTEN promotes EMT and increases chemotherapy resistance in BC cells. Targeting CTEN or the EMT pathway could improve chemosensitivity in treatment-resistant BC, suggesting a novel therapeutic strategy to enhance chemotherapy effectiveness.

C-terminal tensin-like; bladder cancer; drug resistance; epithelial-mesenchymal transition.