NFAT as cancer target: Mission possible?

Article ID	Journal	Published Year	Pages	File Type
8429424	Biochimica et Biophysica Acta (BBA) - Reviews on Cancer	2014	15 Pages	PDF

Abstract

The NFAT signaling pathway regulates various aspects of cellular functions; NFAT acts as a calcium sensor, integrating calcium signaling with other pathways involved in development and growth, immune response, and inflammatory response. The NFAT family of transcription factors regulates diverse cellular functions such as cell survival, proliferation, migration, invasion, and angiogenesis. The NFAT isoforms are constitutively activated and overexpressed in several cancer types wherein they transactivate downstream targets that play important roles in cancer development and progression. Though the NFAT family has been conclusively proved to be pivotal in cancer progression, the different isoforms play distinct roles in different cellular contexts. In this review, our discussion is focused on the mechanisms that drive the activation of various NFAT isoforms in cancer. Additionally, we analyze the potential of NFAT as a valid target for cancer prevention and therapy.

Keywords

ECM DCA NF-κB PI3K nES FOXP3 Jnk HDACs Mmps NFAT CNA TCr ERK PML SRR PGE2 pKa ADP GPCRs IP3 IL-2 BMP4 AICD IP3R angiopoietin-2 GSK3β GM-CSF PLCγ PARP NLS CK1 LPA EWSR1 RHD TonEBP CNB VEGFR AP1 CDK4 CSF1 DSCR1 PIP2 NHD TEM8 Foxc2 forkhead box C2 PROX1 SUMO1 Colony-stimulating factor-1 Calcineurin B AKAP79 prospero homeobox 1 c-Jun Kinase ECs G-protein coupled receptors inositol-1,4,5-triphosphate MAPKs Mitogen activated protein kinases ROS RTKs Ang-2 Adenosine di-phosphate lysophosphatidic acid CSA Interleukin-2 TAD Nuclear localization sequences forkhead box P3 transactivation domain rel-homology domain diacylglycerol DYRK DAG CAM Endothelial cells SOC cyclosporin A Cyclin Dependent Kinase 4 nuclear export signal endoplasmic reticulum Nuclear Factor of Activated T Cells granulocyte-macrophage colony-stimulating factor Transcription factors Fas Ligand FasL Vascular endothelial growth factor Vascular Endothelial Growth Factor (VEGF)nuclear factor-κB phosphatidylinositol 4,5-bisphosphate phospholipase Cγ Promyelocytic leukemia Matrix metalloproteinases activation-induced cell death Small molecule inhibitor Small molecule inhibitors Drug target histone deacetylases activator protein 1 bone morphogenetic protein 4 protein kinase A Prostaglandin E2 poly-ADP-ribose polymerase CdS casein kinase 1 Calmodulin Store-operated calcium channel Calcineurin A Reactive oxygen species IP3 receptor VEGF receptor receptor tyrosine kinases T-cell receptors