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.

Gastrokine 2 Regulates the Antitumor Effect of JAK2/STAT3 Pathway in Gastric Cancer

“…When the mucosa is invaded by bacteria, viruses, or drugs, inflammatory and ulcerative diseases occur, and they play a role in the recovery and regeneration of epithelial cells. TFF1 may act as a tumor suppressor gene in gastric cancer [ 30 , 31 ], esophageal squamous cell carcinoma [ 32 ], and retinoblastoma [ 33 ], while it has been found to be overexpressed in colorectal cancer [ 34 ] and breast cancer [ 35 ]. Low expression of TFF1 may be a marker of poor prognosis in patients with early gastric cancer [ 36 ].…”

CD147 receptor is essential for TFF3-mediated signaling regulating colorectal cancer progression

“… 3 Studies have reported that TFF3 expression is increased during the development and progression of human cancer, including CRC. 4 , 5 In addition, in vitro studies, have shown that TFF3 stimulates survival, proliferation, invasion, and metastasis, and inhibits apoptosis of CRC cells, 6 – 9 indicating that TFF3 regulates key functional characteristics of oncogenesis. However, the precise molecular mechanism by which TFF3 regulates CRC progression remains unclear.…”

A network approach reveals driver genes associated with survival of patients with triple-negative breast cancer

“…TFF1 is a secreted protein normally expressed in gastrointestinal mucosa, with transcriptional regulation by ESR1 and 2 ( Pelden et al., 2013 ). It is well-studied in relation to cancer ( Figure S3 , TFF1 OncoScore = 80) and has been proposed as a biomarker for breast and other cancers ( Wang et al., 2018 ; Yi et al., 2020 ; Yusufu et al., 2019 ; Klett et al., 2018 ). TFF1 gene products were elevated in ER + and PR + BrCa ( Yi et al., 2020 ; Elnagdy et al., 2018 ), whereas they are downregulated in TNBC ( Yi et al., 2020 ).…”