TFF3 and TFF1 expression levels are elevated in colorectal cancer and promote the malignant behavior of colon cancer by activating the EMT process.

Abstract

Reports on the roles of the secreted trefoil factor (TFF)1 and 3 in colorectal cancer (CRC) and their underlying mechanisms of action in tumorigenesis are not common and are controversial. In the present study, the mRNA expression and promoter methylation of TFF1 and TFF3 in cancer and adjacent normal tissues were investigated, and their association with other clinical factors and patient prognosis were evaluated. Moreover, the association between TFF3 and epithelial mesenchymal transition (EMT) was explored by overexpressing or inhibiting TFF3 expression. The results revealed that the mRNA level of TFF1 and TFF3 in the cancer tissues was significantly higher than that in the matched adjacent normal tissues (P=0.034 and P=0.007, respectively), and a higher expression of TFF3, but not TFF1, was predominantly associated with clinicopathological factors and a poorer prognosis. No correlation was observed between promoter methylation and the expression of TFF1 or TFF3. The overexpression of TFF3 promoted the proliferation, migration and invasiveness of HT29 cells, and induced an increase in the expression of Twist1, Snail and Vimentin, while causing a decrease in E-cadherin expression. On the contrary, the knockdown of TFF3 resulted in opposite effects in the LoVo cells. On the whole, the findings of this study indicate that TFF3 may be a promising new factor for the estimation of the survival of patients with CRC, and may promote the malignant progression of CRC by activating the EMT process. Therefore, TFF3 may be a future potential therapeutic target for CRC.