Involvement of epithelial to mesenchymal transition in the development of pancreatic ductal adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an intractable disease as a result of its rapid dissemination and resistance to conventional chemotherapy and radiotherapy. Surgical resection is the only curative therapy, but most of the tumors are unresectable at the time of diagnosis. The molecular mechanisms underlying the biological aggressiveness of this tumor type remain to be clarified. Epithelial to mesenchymal transition (EMT) is a developmental process that leads the phenotype shift from an epithelial morphology to a motile, fibroblast-like morphology. Recent studies showed that EMT is involved in the invasion and metastasis of many types of carcinomas including PDAC. In addition, PDAC cells with the EMT phenotype also exhibit chemoresistance and the cancer stem cell property. Various factors such as cytokines, growth factors, or transcriptional factors were found to promote the EMT program in PDAC cells. In this review, we summarize the current knowledge about the EMT in PDAC cells, focusing on the involvement of this process and its regulatory molecules including microRNA during the development of PDAC cells.

Inflammation and Epithelial-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma: Fighting Against Multiple Opponents

“…Pancreatic ductal adenocarcinoma cell lines BxPC3, L3.6pl, CFPAC-1, and SU86.86 with enhanced E-cadherin expression and reduced expression of the mesenchymal marker Zeb-1 display sensitivity to the chemotherapeutic agents 5-FU, gemcitabine, and cisplatin, whereas other cell lines Hs766T, Panc-1, MiaPaCa-2, AsPC-1, and MPanc96 express low E-cadherin, high Zeb-1 levels and display EMT as well as exhibit resistance to the aforementioned chemotherapeutic drugs 101. Zeb-1 downregulation in PDAC cells with EMT phenotype enhances the expression of epithelial markers and retrieve drug sensitivity, indicating the involvement of Zeb-1 and other EMT regulators in enhancing the resistance of PDAC cells to chemotherapy 102. This notion was further validated in an in vivo mouse model.…”

Inhibition of S-Adenosylmethionine-Dependent Methyltransferase Attenuates TGFβ1-Induced EMT and Metastasis in Pancreatic Cancer: Putative Roles of miR-663a and miR-4787-5p

“…The tendency of pancreatic tumors to metastasize to lymph nodes, the abdominal cavity, and the liver at a very early stage compromises the effectiveness of chemotherapeutic agents (1, 2). Hence, challenges to prevent tumor spread and drug resistance continue to exist for pancreatic cancer treatment.…”

“…Evidence shows EMT, distinct cellular events characterized by loss of epithelial phenotypes and gain of mesenchymal phenotypes, contributes to the early dissemination of primary tumor cells and metastatic spread (2–4). Further, the process of EMT itself has been shown to promote stem-like characteristics of tumor cells and increase drug resistance (2–4). Therefore, therapeutic strategies directed against EMT would likely prove useful in controlling metastasis and drug resistance in PDAC patients.…”

The Lncrna-TUG1/EZH2 Axis Promotes Pancreatic Cancer Cell Proliferation, Migration and EMT Phenotype Formation Through Sponging Mir-382

“…Early metastasis is one of the characteristics of pancreatic cancer, which always results in a poor curative effect or chemotherapy failure. Epithelial-to-mesenchymal (EMT), a process of losing epithelial phenotypes and gaining mesenchymal phenotypes, contributes to the early dissemination of primary tumor cells and metastatic spread [4-6]. The aim of our present study is to explore the underlying EMT formation mechanism of PC and potential therapeutic value.…”