Redox signaling-mediated tumor extracellular matrix remodeling: pleiotropic regulatory mechanisms.

Abstract

The extracellular matrix (ECM), a fundamental constituent of all tissues and organs, is crucial for shaping the tumor microenvironment. Dysregulation of ECM remodeling has been closely linked to tumor initiation and progression, where specific signaling pathways, including redox signaling, play essential roles. Reactive oxygen species (ROS) are risk factors for carcinogenesis whose excess can facilitate the oxidative damage of biomacromolecules, such as DNA and proteins. Emerging evidence suggests that redox effects can aid the modification, stimulation, and degradation of ECM, thus affecting ECM remodeling. These alterations in both the density and components of the ECM subsequently act as critical drivers for tumorigenesis. In this review, we provide an overview of the functions and primary traits of the ECM, and it delves into our current understanding of how redox reactions participate in ECM remodeling during cancer progression. We also discuss the opportunities and challenges presented by clinical strategies targeting redox-controlled ECM remodeling to overcome cancer. The redox-mediated ECM remodeling contributes importantly to tumor survival, progression, metastasis, and poor prognosis.A comprehensiveinvestigationof the concrete mechanism of redox-mediatedtumor ECM remodeling and the combination usage of redox-targeted drugs withexisting treatment meansmay revealnew therapeutic strategyfor future antitumor therapies.