Bidirectional regulation of the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon gene pathway and its impact on hepatocellular carcinoma.

BACKGROUND

Hepatocellular carcinoma (HCC) ranks as the fourth leading cause of cancer-related deaths in China, and the treatment options are limited. The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) activates the stimulator of interferon gene (STING) signaling pathway as a crucial immune response pathway in the cytoplasm, which detects cytoplasmic DNA to regulate innate and adaptive immune responses. As a potential therapeutic target, cGAS-STING pathway markedly inhibits tumor cell proliferation and metastasis, with its activation being particularly relevant in HCC. However, prolonged pathway activation may lead to an immunosuppressive tumor microenvironment, which fostering the invasion or metastasis of liver tumor cells.

AIM

To investigate the dual-regulation mechanism of cGAS-STING in HCC.

METHODS

This review was conducted according to the PRISMA guidelines. The study conducted a comprehensive search for articles related to HCC on PubMed and Web of Science databases. Through rigorous screening and meticulous analysis of the retrieved literature, the research aimed to summarize and elucidate the impact of the cGAS-STING pathway on HCC tumors.

RESULTS

All authors collaboratively selected studies for inclusion, extracted data, and the initial search of online databases yielded 1445 studies. After removing duplicates, the remaining 964 records were screened. Ultimately, 55 articles met the inclusion criteria and were included in this review.

CONCLUSION

Acute inflammation can have a few inhibitory effects on cancer, while chronic inflammation generally promotes its progression. Extended cGAS-STING pathway activation will result in a suppressive tumor microenvironment.