Abstract: Matrix stiffness and fluid shear force are key mechanical cues in ovarian cancer microenvironment that can impact cancer stemness, tumorigenicity and metastasis. However, the molecular identity of mechanosensor and/or mechanosensitive mediator that can be respond to matrix stiffness and fluid shear force is unclear. TRPV4 is a mechanosensitive Ca2+-permeable channel. In the present study, we found that soft matrix can increase the expression level of TRPV4, subsequently stimulating the growth of ovarian cancer stem cells (OCSC), elevating the expression level of multiple cancer stem cell (CSC) markers, and promoting tumor xenograft growth. Furthermore, fluid shear force can directly stimulate the activity of TRPV4 channels, consequently elevating the expression level of multiple CSC markers, promoting migration of OCSCs in vitro and peritoneal tumor metastasis in vivo. Taken together, TRPV4 is a key mechanosensor (or mechanosensitive mediator) that responds to matrix softness and fluid shear force in ovarian cancer progression.
