The cGAS paradox: Contrasting roles for CGAS-sting pathway in chromosomal instability

Abstract

Chromosomal instability (CIN) is an intricate phenomenon that is often found in human cancer, characterized by persisting errors in chromosome segregation. This ongoing chromosome mis-segregation results in structural and numerical chromosomal abnormalities that have been widely described to promote tumor evolution. In addition to being a driver of tumor evolution, recent evidence demonstrates CIN to be the central node of the crosstalk between a tumor and its surrounding microenvironment, as mediated by the cGAS-STING pathway. The role that cGAS-STING signaling exerts on CIN tumors is both complex and paradoxical. On one hand, the cGAS-STING axis promotes the clearance of CIN tumors through recruitment of immune cells, thus suppressing tumor progression. On the other hand, the cGAS-STING pathway has been described to be the major regulator in the promotion of metastasis of CIN tumors. Here, we review this dual role of the cGAS-STING pathway in the context of chromosomal instability and discuss the potential therapeutic implications of cGAS-STING signaling for targeting CIN tumors.