NFAT as cancer target: mission possible?

Biochim Biophys Acta. 2014 Dec;1846(2):297-311. doi: 10.1016/j.bbcan.2014.07.009. Epub 2014 Jul 26.

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: Calcineurin–NFAT signaling; Cancer development and progression; Drug target; NFAT; NFAT regulation; Small molecule inhibitor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Disease Progression
  • Homeostasis
  • Humans
  • NFATC Transcription Factors / antagonists & inhibitors
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / physiology*
  • Neoplasm Metastasis
  • Neoplasms / drug therapy
  • Neoplasms / pathology*
  • Protein Isoforms
  • Signal Transduction
  • Tumor Microenvironment

Substances

  • NFATC Transcription Factors
  • Protein Isoforms