Cellular senescence and senescence-associated secretory phenotype via the cGAS-STING signaling pathway in cancer

Abstract

Cellular senescence is historically regarded as a tumor suppression mechanism to prevent damaged cells from aberrant proliferation in benign and premalignant tumors. However, recent findings have suggested that senescent cells contribute to tumorigenesis and age-associated pathologies through the senescence-associated secretory phenotype (SASP). Therefore, to control age-associated cancer, it is important to understand the molecular mechanisms of the SASP in the cancer microenvironment. New findings have suggested that the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway, a critical indicator of innate immune response, triggers the SASP in response to accumulation of cytoplasmic DNA (cytoplasmic chromatin fragments, mtDNA and cDNA) in senescent cells. Notably, the cGAS-STING signaling pathway promotes or inhibits tumorigenesis depending on the biological context in vivo, indicating that it may be a potential therapeutic target for cancer. Herein, we review the regulatory machinery and biological function of the SASP via the cGAS-STING signaling pathway in cancer.

Keywords: DNA damage; SASP; cGAS-STING; cellular senescence; tumorigenesis.