Piezo Family: From Structure to Therapeutic Agents in Cancer

Mechanotransduction, converting physical forces into biochemical signals, has emerged as a key regulatory mechanism in cancer. The Piezo family (Piezo1 and Piezo2) is critical mechanically activated ion channels that transduce mechanical stimuli into intracellular calcium flux, influencing proliferation, migration, and differentiation. Emerging evidence strongly implicates their dysregulation in shaping cancer phenotypes and remodeling of the tumor microenvironment. Altered Piezo expression occurs in multiple malignancies (e.g., breast, lung, and colorectal cancer), correlating with progression, metastasis, and clinical outcomes. Piezo channels also intersect with immune and angiogenic pathways, extending the mechanical influence to the tumor ecosystem. Thus, Piezos act as central integrators of tumor physiology by integrating mechanical stress with biochemical and immune signaling. However, translating Piezo-targeted interventions into clinical practice remains challenging. This perspective summarizes current understanding of Piezos' structure and gating, their roles in cancer, and the opportunities and obstacles for Piezo-based therapy, aiming to delineate future translational pathways.