Primers on molecular pathways - The NFAT transcription pathway in pancreatic cancer

The calcineurin-responsive nuclear factor of activated T cells (NFAT) family of transcription factors was originally identified as a group of inducible nuclear proteins, which regulate transcription during T lymphocyte activation. However, following their initial discovery, a multitude of studies quickly established that NFAT proteins are also expressed in cells outside the immune system, where they participate in the regulation of the expression of genes influencing cell growth and differentiation. Ectopic activation of individual NFAT members is now recognized as an important aspect for oncogenic transformation in several human malignancies, most notably in pancreatic cancer. Sustained activation of the Ca²⁺/calcineurin/NFAT signaling pathway has emerged as a powerful regulatory principle governing pancreatic cancer cell growth. Activated NFAT proteins form complexes with key oncogenic proteins to regulate the transcription of master cell cycle regulators and proteins with functions in cell survival, migration and angiogenesis. This review pays particular attention to recent advances in our understanding of how the NFAT transcription pathway controls gene expression during development and progression of pancreatic cancer.