GSK-3β Governs Inflammation-Induced NFATc2 Signaling Hubs to Promote Pancreatic Cancer Progression.

ABSTRACT: We aimed to investigate the mechanistic, functional, and therapeutic role of glycogen synthase kinase 3β (GSK-3β) in the regulation and activation of the proinflammatory oncogenic transcription factor nuclear factor of activated T cells (NFATc2) in pancreatic cancer. IHC, qPCR, immunoblotting, immunofluorescence microscopy, and proliferation assays were used to analyze mouse and human tissues and cell lines. Protein-protein interactions and promoter regulation were analyzed by coimmunoprecipitation, DNA pulldown, reporter, and ChIP assays. Preclinical assays were performed using a variety of pancreatic cancer cells lines, xenografts, and a genetically engineered mouse model (GEMM). GSK-3β-dependent SP2 phosphorylation mediates NFATc2 protein stability in the nucleus of pancreatic cancer ce

SUBMITTER: Baumgart S 

PROVIDER: S-EPMC6071313 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature