Gordon et al (52) reported that loss of type III TGF-β receptor expression increased Navitoclax motility and invasiveness associated with EMT during PC progression. Wang et al. (45) reported

that Notch-2 and its ligand, Jagged-1, were highly upregulated in gemcitabine-resistant PC cells. The finding is consistent with the role of the Notch signaling pathway in the acquisition of EMT phenotype. Down-regulation of Notch signaling pathway not only decreased invasive behavior of the drug-resistant cells but also led to partial reversal of the EMT phenotype, resulting in the MET, which was associated with decreased expression of vimentin, Zeb-1, Slug, Snail, and Inhibitors,research,lifescience,medical NF-κB (45). Their findings therefore provide a direct evidence of the association between EMT and PC invasiveness. In a recent study, Haque et al. (53) reported that Cyr61/CCN1 signaling is critical for EMT and promotes pancreatic carcinogenesis. Cyr61 (cysteine-rich 61) is a member of the CCN family of growth factors that includes CTGF, NOV, WISP-1,

WISP-2 and WISP-3. Cyr61 is Inhibitors,research,lifescience,medical known to link cell surface and extracellular matrix and plays important roles on cell adhesion, proliferation, migration, differentiation, and angiogenesis during normal developmental and pathological processes (54). Inhibitors,research,lifescience,medical Cyr61 expression was detected in the early PC precursor lesions and its expression intensified with disease progression. Upon Cyr61 silencing, the aggressive behaviors of PC were reduced by obliterating interlinking events such as reversing EMT, blocking the expression of stem-cell-like traits and inhibiting migration. In contrast, addition of Cyr61 augmented EMT and stemness Inhibitors,research,lifescience,medical features in relatively less aggressive PC cells (53). Taken together, PC with EMT features has more aggressive behaviors and is associated

with poor patient survival. Multiple proteins and signaling pathways are involved in this process. Reversal of EMT phenotype could potentially reduce PC invasiveness and Inhibitors,research,lifescience,medical hence prevent metastasis. Conclusion Accumulating evidences suggest that EMT plays important roles in PC progression through several plausible mechanisms. PC cells may acquire stemness properties and become drug resistant during undergoing EMT. PC with EMT features is more aggressive and is associated with poor patient survival. Future strategies that specifically target against EMT phenotype could potentially reduce tumoral drug resistance Liothyronine Sodium and invasiveness and hence prolong the survival of patients with PC. Footnotes No potential conflict of interest.
Pancreatic cancer is the 10th most commonly diagnosed cancer and the 4th leading cause of cancer death in the U.S. An estimated 43,140 new cases were diagnosed and 36,800 deaths occurred in the U.S. in 2010. The survival rate for this deadly disease has not improved substantially in nearly the last 40 years even with aggressive treatment. For all stages combined, the 1 and 5-year relative survival rates are 25% and 6%, respectively.