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.

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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