Here, we tested two drugs displaying dual inhibitory activity towards PDK1 and Aurora kinase A in a panel of pancreatic cancer cell lines and in two in vivo models of pancreatic cancer.
Aurora Kinase A (AKA) is over-expressed in pancreatic cancer (PC) and controls G2-M transition during mitosis and AKA inhibitors have been developed that induce mitotic arrest.
Phospho-resistant ALDH1A1 fully reverses EMT and CSC phenotypes, thus serving as dominant negative, which underscores the clinical significance of the AURKA-ALDH1A1 signaling axis in pancreatic cancer.
We uncovered a crucial role for the Aurora kinase A (AURKA)-Twist1 axis in promoting epithelial-to-mesenchymal transition (EMT) and chemoresistance in pancreatic cancer.
These results indicate that AURKA is a direct target of the MAPK pathway and that its overexpression in pancreatic cancer is induced by hyperactivation of the pathway, at least via ETS2.
These results indicate that inhibition of AURKA expression can result in potent antitumor activity and chemosensitizing activity to taxanes in human pancreatic cancer.
Antisense nucleotides specifically targeted at Aurora-2 arrest the cell cycle in pancreatic cancer cells, indicating the potential of Aurora-2 as a therapeutic target in pancreatic cancer.