Yes-associated protein 1 in cancer: bridging mechanical transduction and epigenetic regulation

Yes-associated protein 1 (YAP1) and its paralog TAZ serve as central mechanotransductive transcription coactivators that integrate mechanical cues from the extracellular matrix, such as stiffness and fluid shear stress, with epigenetic modifications to drive oncogenic processes. They regulate diverse biological functions, including proliferation, metastasis, immune evasion, autophagy, ferroptosis, and metabolism. This review highlights how YAP1/TAZ signaling is modulated by mechanosensitive pathways (Integrin/FAK, Rho GTPases) and epigenetic mechanisms (m6A methylation, DNA methylation), contributing to therapy resistance and disease progression. Targeting the mechano-epigenetic axis of YAP1/TAZ offers promising therapeutic strategies for cancer treatment.