Tumor microenvironment and mechanotransduction pathways: Novel targets and new directions for cancer therapy

In cancer research, the extracellular matrix (ECM) of the tumor microenvironment (TME) was once regarded as a mere passive structural scaffold for tumor tissue, while the biomechanical cues generated by its dynamic physical remodeling have now emerged as crucial active regulators that drive tumor initiation, progression and metastasis. By sensing and transducing these abnormal mechanical signals (e.g., matrix stiffness, fluid shear stress) through four core mechanotransduction mechanisms (mechanosensitive ion channels, adhesive complexes, nuclear mechanotransducers, and cytoskeletal dynamics), tumor cells convert them into intracellular biochemical responses. This review begins with the ECM within the TME, exploring mechanosensing and mechanotransduction in the TME, to construct a multi-dimensional research system integrating ECM abnormal remodeling, core mechanotransduction mechanisms and the multi-faceted regulatory effects of mechanical signals on tumor progression. Furthermore, it discusses the application of biomechanical cues in clinical tumor diagnosis, as well as attempts at anti-tumor therapies involving artificial intervention in ECM components to alter its physical properties, thereby providing reference ideas for biomechanical research.