cGAS/STING cross-talks with cell cycle and potentiates cancer immunotherapy

Mol Ther. 2022 Mar 2;30(3):1006-1017. doi: 10.1016/j.ymthe.2022.01.044. Epub 2022 Feb 2.

Abstract

The correct duplication and transfer of genetic material to daughter cells is the major event of cell division. Dysfunction of DNA replication or chromosome segregation presents challenges in cancer initiation and development as well as opportunities for cancer treatment. Cyclic GMP-AMP synthase (cGAS) of the innate immune system detects cytoplasmic DNA and mediates downstream immune responses through the molecule stimulator of interferon genes (STING). However, how cytosolic DNA sensor cGAS participates in guaranteeing accurate cell division and preventing tumorigenesis is still unclear. Recent evidence indicates malfunction of cGAS/STING pathway in cancer progression. Cell cycle-targeted therapy synergizes with immunotherapy via cGAS/STING activation, leading to promising therapeutic benefit. Here, we review the interactions between cell cycle regulation and cGAS/STING signaling, thus enabling us to understand the role of cGAS/STING in cancer initiation, development, and treatment.

Keywords: cGAS/STING; cell cycle; immunotherapy; tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Cycle / genetics
  • Cell Division
  • DNA / metabolism
  • Humans
  • Immunity, Innate
  • Immunotherapy
  • Membrane Proteins* / metabolism
  • Neoplasms* / genetics
  • Neoplasms* / therapy
  • Nucleotidyltransferases / genetics
  • Nucleotidyltransferases / metabolism

Substances

  • Membrane Proteins
  • DNA
  • Nucleotidyltransferases