TGFβ1-induced cell motility is mediated through Cten in colorectal cancer

Cten is a tensin which promotes epithelial-mesenchymal transition (EMT) and cell motility. The precise mechanisms regulating Cten are unknown, although Cten could be regulated by several cytokines and growth factors. Since Transforming growth factor beta 1 (TGF-{beta}1) regulates integrin function and promotes EMT / cell motility, we investigated whether this happens through Cten signalling in colorectal cancer (CRC).\n\nTGF-{beta}1 signalling was modulated by either stimulation or knockdown in the CRC cell lines SW620 and HCT116. The effect of this modulation on expression of Cten, EMT markers and cellular function was tested. Cten role as a direct mediator of TGF-{beta}1 signalling was investigated in a CRC cell line with a deleted Cten gene (SW620{Delta}Cten).\n\nWhen TGF-{beta}1 was stimulated or inhibited, this resulted in, respectively, upregulation and downregulation of Cten expression and EMT markers. Cell migration and invasion were significantly increased following TGF-{beta}1 stimulation and lost by TGF-{beta}1 knockdown. TGF-{beta}1 stimulation in SW620{Delta}Cten resulted in selective loss of the effect of TGF-{beta}1 signalling on EMT and cell motility whilst the stimulatory effect on cell proliferation was retained.\n\nThese data suggested Cten may play an essential role in mediating TGF-{beta}1-induced EMT and cell motility and may play a role in metastasis in CRC.