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Updated: Feb 10, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
Trefoil factor 1 inhibits epithelial-mesenchymal transition of pancreatic intraepithelial neoplasm
Junpei Yamaguchi1, Yukihiro Yokoyama1, Toshio Kokuryo1
1Division of Surgical Oncology, Department of Surgery, and.
Abstract:
The tumor-suppressive role of trefoil factor family (TFF) members in gastric carcinogenesis has been suggested, but their significance and mechanisms in other digestive diseases remain elusive. To clarify the role of TFF1 in pancreatic carcinogenesis, we performed IHC on human samples, transfected siRNA against TFF1 into pancreatic cancer cell lines, and employed mouse models in which PanIN development and loss of TFF1 occur simultaneously. In human samples, the expression of TFF1 was specifically observed in pancreatic intraepithelial neoplasm (PanIN), but was frequently lost in the invasive component of pancreatic ductal adenocarcinoma (PDAC). When the expression of TFF1 was suppressed in vitro, pancreatic cancer cell lines showed enhanced invasive ability and features of epithelial-mesenchymal transition (EMT), including upregulated Snail expression. TFF1 expression was also observed in PanIN lesions of Pdx-1 Cre; LSL-KRASG12D (KC) mice, a model of pancreatic cancer, and loss of TFF1 in these mice resulted in the expansion of PanIN lesions, an EMT phenotype in PanIN cells, and an accumulation of cancer-associated fibroblasts (CAFs), eventually resulting in the development of invasive adenocarcinoma. This study indicates that the acquisition of TFF1 expression is an early event in pancreatic carcinogenesis and that TFF1 might act as a tumor suppressor to prevent EMT and the invasive transformation of PanIN.
Insights
Trefoil Factor Family 1 (TFF1) acts as a tumor suppressor in pancreatic cancer. Its loss promotes invasive growth and epithelial-mesenchymal transition (EMT) in pancreatic intraepithelial neoplasia (PanIN).
Area of Science:
- Oncology
- Gastroenterology
- Molecular Biology
Background:
- The tumor-suppressive role of Trefoil Factor Family (TFF) members is known in gastric cancer, but their function in pancreatic carcinogenesis is unclear.
- Understanding TFF1's role is crucial for developing strategies against pancreatic ductal adenocarcinoma (PDAC).
Purpose of the Study:
- To investigate the role and mechanism of TFF1 in pancreatic carcinogenesis.
- To clarify TFF1's function in the progression from pancreatic intraepithelial neoplasia (PanIN) to invasive PDAC.
Main Methods:
- Immunohistochemistry (IHC) on human pancreatic tissue samples.
- In vitro studies using siRNA to suppress TFF1 in pancreatic cancer cell lines.
- In vivo studies using genetically engineered mouse models (Pdx-1 Cre; LSL-KRASG12D) that develop PanIN and allow for TFF1 loss.
Main Results:
- TFF1 expression was detected in PanIN but frequently lost in invasive PDAC.
- TFF1 suppression in vitro enhanced cancer cell invasion and induced epithelial-mesenchymal transition (EMT) with increased Snail expression.
- TFF1 loss in mouse models led to expanded PanIN, EMT, cancer-associated fibroblast (CAF) accumulation, and invasive adenocarcinoma development.
Conclusions:
- TFF1 expression is an early event in pancreatic carcinogenesis.
- TFF1 functions as a tumor suppressor by inhibiting EMT and the invasive transformation of PanIN.
- Loss of TFF1 contributes to the progression of pancreatic cancer.
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