TGFβ1-induced cell motility but not cell proliferation is mediated through Cten in colorectal cancer

Asiri, Abdulaziz; Raposo, Teresa Pereira; Alfahed, Abdulaziz; Ilyas, Mohammad

Abstract

Cten (C-terminal tensin-like) is a member of the tensin protein family found in complex with integrins at focal adhesions. It promotes epithelial‐mesenchymal transition (EMT) and cell motility. The precise mechanisms regulating Cten are unknown, although we and others have shown that Cten could be under the regulation of several cytokines and growth factors. Since Transforming growth factor beta 1 (TGF-β1) regulates integrin function and promotes EMT / cell motility, we were prompted to investigate whether TGF-β1 induces EMT and cell motility through Cten signalling in colorectal cancer.

TGF-β1 signalling was modulated by either stimulation with TGF-β1 or knockdown of TGF-β1 in the CRC cell lines SW620 and HCT116. The effect of this modulation on expression of Cten, EMT markers and on cellular function was tested. The role of Cten as a direct mediator of TGF-β1 signalling was investigated in a CRC cell line in which the Cten gene had been deleted (SW620ΔCten).

When TGF-β1 was stimulated or inhibited, this resulted in, respectively, upregulation and downregulation of Cten expression and EMT markers (Snail, Rock, N-Cadherin, Src). Cell migration and cell invasion were significantly increased following TGF-β1 stimulation and lost by TGF-β1 knockdown. TGF-β1 stimulation of the SW620ΔCten cell line resulted in selective loss of the effect of TGF-β1 signalling pathway on EMT and cell motility whilst the stimulatory effect on cell proliferation was retained.

These data suggested Cten may play an essential role in mediating TGF-β1 induced EMT and cell motility and may therefore play a role in metastasis in CRC.

Citation

Asiri, A., Raposo, T. P., Alfahed, A., & Ilyas, M. (2018). TGFβ1-induced cell motility but not cell proliferation is mediated through Cten in colorectal cancer. International Journal of Experimental Pathology, 99(6), 323-330. https://doi.org/10.1111/iep.12300

• Journal Article Type: Article
• Acceptance Date: Dec 6, 2018
• Online Publication Date: Jan 15, 2019
• Publication Date: Dec 1, 2018
• Deposit Date: Jan 24, 2019
• Publicly Available Date: Dec 2, 2019
• Journal: International Journal of Experimental Pathology
• Print ISSN: 0959-9673
• Electronic ISSN: 1365-2613
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 99
• Issue: 6
• Pages: 323-330
• DOI: https://doi.org/10.1111/iep.12300
• Keywords: Epithelial‐mesenchymal transition (EMT); Colorectal cancer; Transforming growth factor beta (TGF‐β); Cell motility; Cell invasion
• Public URL: https://nottingham-repository.worktribe.com/output/1495029
• Publisher URL: https://onlinelibrary.wiley.com/doi/full/10.1111/iep.12300
• Contract Date: Jan 25, 2019