Epithelial-Mesenchymal Transition in Pancreatic Cancer: A Review

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies and is characterized by its insensitivity to current therapy. The invasion and metastasis of solid tumors such as PDAC are complex processes involving many factors. Recent insights into the role of cancer stem cells (CSCs) and the epithelial-mesenchymal transition (EMT) in tumorigenesis have increased the knowledge base and highlighted new therapeutic targets of this disease. The process of EMT is regulated by a complex network of cytokines, transcription factors, growth factors, signaling pathways, and the tumor microenvironment, exhibiting CSC-like properties. The transition of solid cancer cells from an epithelial to a mesenchymal phenotype increases their migratory and invasive properties, thus promoting metastasis. In PDAC, the exact influence of EMT on the biological behaviors of cancer cells and its impact on clinical therapy remain controversial, but the therapeutic strategy of combining EMT inhibition with chemotherapy deserves attention. Alternatively, anti-inflammatory therapy that targets the interaction between inflammation and EMT is a valid strategy for treating the premalignant stage of tumor progression. In this review, we summarize the latest research on EMT and the potential relationship between EMT and PDAC.

<p>Paeonol Inhibits Pancreatic Cancer Cell Migration and Invasion Through the Inhibition of TGF-β1/Smad Signaling and Epithelial-Mesenchymal-Transition</p>

“…33,34 Various signaling pathways are involved in the induction of EMT, include TGF-β1, Wnt-β-catenin, Notch, Hedgehog, and tyrosine kinases. 32,35 TGF-β1 is an inflammatory cytokine and a promoter and supporter of EMT. 36 In PDAC, TGF-β1 has been shown to induce EMT and association between TGF-β1 induced gene expression and clinical outcomes have been described.…”

Axl-mediated activation of TBK1 drives epithelial plasticity in pancreatic cancer

“…It is estimated that nearly 90% of cancer mortalities are due to metastases [35], yet TBK1 studies to date have evaluated the effect of TBK1 inhibition only on primary tumor burden. EMT is a hallmark of metastasis in pancreatic cancer and is critical to cancer cell dissemination [36][37][38]. Within this morphological cellular program, epithelial cancer cells lose contact with the basement membrane and neighboring cells while gaining a more mesenchymal and invasive phenotype [36,39].…”

Cancer stem cells and mesenchymal stem cells in pancreatic ductal adenocarcinoma

“…Активную роль в развитии ЭМП панкреатических РСК играет Sonic hedgehog сигнальный путь [19]. По данным S. Wang et al (2017), посредством ЭМП РСК панкреатической протоковой карциномы приобретают агрессивный мезенхимальный фенотип, обеспечивающий возможность быстрого распространения трансформированных клеток [43], а также способность к миграции и метастазированию раковых клеток [28]. По данным D. M. , активация МСК в строме ПАПЖ ассоциирована с возрастанием экспрессии матриксных металлопротеиназ 2 и 9 типа, что является неотъемлемым компонентом реализации инвазивных свойств опухоли [37].…”