Cellular senescence and senescence-associated secretory phenotype via the cGAS-STING signaling pathway in cancer.
Tze Mun LooKenichi MiyataYoko TanakaAkiko TakahashiPublished in: Cancer science (2019)
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.
Keyphrases
- signaling pathway
- papillary thyroid
- induced apoptosis
- immune response
- dna damage
- squamous cell
- endothelial cells
- stem cells
- epithelial mesenchymal transition
- transcription factor
- stress induced
- escherichia coli
- gene expression
- lymph node metastasis
- endoplasmic reticulum stress
- young adults
- squamous cell carcinoma
- cystic fibrosis
- risk assessment
- pseudomonas aeruginosa
- cell death
- inflammatory response
- protein kinase
- nucleic acid