Περίληψη:
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.
Συγγραφείς:
Palamaris, Kostas
Felekouras, Evangelos
Sakellariou, Stratigoula
