Dec 20, 2019

The Cytosolic DNA-Sensing cGAS-STING Pathway in Cancer

Cancer Discovery
John Kwon, Samuel F Bakhoum

Abstract

The recognition of DNA as an immune-stimulatory molecule is an evolutionarily conserved mechanism to initiate rapid innate immune responses against microbial pathogens. The cGAS-STING pathway was discovered as an important DNA-sensing machinery in innate immunity and viral defense. Recent advances have now expanded the roles of cGAS-STING to cancer. Highly aggressive, unstable tumors have evolved to co-opt this program to drive tumorigenic behaviors. In this review, we discuss the link between the cGAS-STING DNA-sensing pathway and antitumor immunity as well as cancer progression, genomic instability, the tumor microenvironment, and pharmacologic strategies for cancer therapy. SIGNIFICANCE: The cGAS-STING pathway is an evolutionarily conserved defense mechanism against viral infections. Given its role in activating immune surveillance, it has been assumed that this pathway primarily functions as a tumor suppressor. Yet, mounting evidence now suggests that depending on the context, cGAS-STING signaling can also have tumor and metastasis-promoting functions, and its chronic activation can paradoxically induce an immune-suppressive tumor microenvironment.

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Mentioned in this Paper

Cancer Treatment
Neoplasms
Malignant Neoplasms
Tumorigenicity
Chromogranin A
Cancer Progression
Virus Diseases
DNA
Genomic Instability
Sp1 Transcription Factor

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