Our data indicate that targeting both MDM2 and NFAT1 represents a novel and effective strategy to treat pancreatic cancer.<b>Significance:</b> These findings suggest that pharmacological inhibition of both MDM2 and NFAT1 is a promising strategy for the treatment of pancreatic cancer, even in tumors lacking functional p53.<i></i>.
Conversely, inactivation of NFATc2 disrupts this repressor complex assembly and local heterochromatin formation, resulting in restoration of p15(INK4b) expression and inhibition of pancreatic cancer growth in vitro and in vivo.
Here, we demonstrate the existence of a nuclear GSK-3β-NFATc2 stabilization pathway that promotes breast and pancreatic cancer growth in vitro and in vivo and serves as a bona fide target of zoledronic acid.