Interplay between signal transducers and activators of transcription (STAT) proteins and cancer: involvement, therapeutic and prognostic perspective

Clin Exp Med. 2023 Dec;23(8):4323-4339. doi: 10.1007/s10238-023-01198-8. Epub 2023 Sep 29.

Abstract

Signal transducers and activators of transcription or STAT are proteins that consist of various transcription factors that are responsible for activating genes regarding cell proliferation, differentiation, and apoptosis. They commonly activate several cytokine, growth, or hormone factors via the JAK-STAT signaling pathway by tyrosine phosphorylation which are responsible for giving rise to numerous immune responses. Mutations within the Janus-Kinases (JAKs) or the STATs can set off the commencement of various malfunctions of the immune system of the body; carcinogenesis being an inevitable outcome. STATs are known to act as both oncogenes and tumor suppressor genes which makes it a hot topic of investigation. Various STATs related mechanisms are currently being investigated to analyze its potential of serving as a therapeutic base for numerous immune diseases and cancer; a deeper understanding of the molecular mechanisms involved in the signaling pathways can contribute to the same. This review will throw light upon each STAT member in causing cancer malignancies by affecting subsequent signaling pathways and its genetic and epigenetic associations as well as various inhibitors that could be used to target these pathways thereby devising new treatment options. The review will also focus upon the therapeutic advances made in cancers that most commonly affect people and discuss how STAT genes are identified as prognostic markers.

Keywords: Carcinogenesis; JAK-STAT signaling pathway; Prognosis; STATs; Therapeutics.

Publication types

  • Review

MeSH terms

  • DNA-Binding Proteins
  • Humans
  • Neoplasms* / diagnosis
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Prognosis
  • Protein-Tyrosine Kinases* / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism

Substances

  • Protein-Tyrosine Kinases
  • Trans-Activators
  • DNA-Binding Proteins