Navigating the cGAS-STING signaling pathway in breast cancer: Reinterpreting the paradox of antitumor and pro-metastatic.

Abstract

The cGAS-STING signaling pathway exhibits functions in breast cancer that include both antitumor immunity and pro-metastatic inflammation, transcending traditional linear switch models. To address this cognitive bottleneck, this paper proposes the conceptual framework of "cGAS-STING pathway-guided signal flow." It attributes pathway outcomes to multi-level fine-tuning, aiming to decipher initial immunogenic/pathogenic signals in the upstream phase based on intensity, duration, and origin. It elucidates how the STING protein, as a central hub, integrates and programs signals through a complex network of post-translational modifications at the midstream, thereby determining whether downstream effector branching favors the IFN-I-mediated antitumor axis or the NF-κB-driven pro-metastatic inflammatory axis. Based on this framework, this paper examines the key checkpoints at each level to explore in depth how to precisely regulate the cGAS-STING signaling pathway in order to maximize antitumor immune responses while mitigating potential risks of metastasis. This navigational framework clarifies signal branching mechanisms between the IFN-I antitumor axis and the NF-κB metastasis-promoting axis in breast cancer, identifies key nodes in signal branching, and evaluates the STING regulatory characteristics of various molecular subtypes. This provides both theoretical and practical foundations for signal reprogramming interventions, patient stratification, and the optimization of combination therapies.