Palamaris Kostas, Felekouras Evangelos, Sakellariou Stratigoula
1ST Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
1ST Department of Surgery, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Cancers (Basel). 2021 Nov 4;13(21):5532. doi: 10.3390/cancers13215532.
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies, characterized by aggressive biological behavior and a lack of response to currently available chemotherapy. Emerging evidence has identified epithelial to mesenchymal transition (EMT) as a key driver of PDAC progression and a central regulator in the development of drug resistance. EMT is a reversible transdifferentiation process controlled by complex interactions between multiple signaling pathways such as TGFb, Wnt, and Notch, which converge to a network of specific transcription factors. Activation of EMT transcriptional reprogramming converts cancer cells of epithelial differentiation into a more mesenchymal phenotypic state. EMT occurrence in pre-invasive pancreatic lesions has been implicated in early PDAC dissemination. Moreover, cancer cell phenotypic plasticity driven by EMT contributes to intratumoral heterogeneity and drug tolerance and is mechanistically associated with the emergence of cells exhibiting cancer stem cells (CSCs) phenotype. In this review we summarize the available data on the signaling cascades regulating EMT and the molecular isnteractions between pancreatic cancer and stromal cells that activate them. In addition, we provide a link between EMT, tumor progression, and chemoresistance in PDAC.
胰腺导管腺癌（PDAC）是最致命的恶性肿瘤之一，其特征为具有侵袭性的生物学行为且对目前可用的化疗无反应。新出现的证据已将上皮-间质转化（EMT）确定为PDAC进展的关键驱动因素以及耐药性发展的核心调节因子。EMT是一个可逆的转分化过程，受多种信号通路（如转化生长因子β、Wnt和Notch）之间复杂相互作用的控制，这些信号通路汇聚到一个特定转录因子网络。EMT转录重编程的激活将上皮分化的癌细胞转化为更具间充质表型的状态。EMT在胰腺浸润前病变中的发生与早期PDAC扩散有关。此外，由EMT驱动的癌细胞表型可塑性导致肿瘤内异质性和药物耐受性，并且在机制上与表现出癌症干细胞（CSC）表型的细胞出现相关。在本综述中，我们总结了关于调节EMT的信号级联以及激活它们的胰腺癌细胞与基质细胞之间分子相互作用的现有数据。此外，我们阐述了EMT、肿瘤进展和PDAC化疗耐药性之间的联系。
