Mechanobiology of solid tumor vasculature: implications for tumor progression

Under normal physiological conditions, the vasculature forms a selective barrier that regulates molecular and cellular transport, largely maintained through vascular endothelial cadherin (VE-cadherin)-mediated junctions formed by endothelial cells. However, in the tumor microenvironment (TME) of solid tumors, the vasculature is disrupted due to biochemical and mechanical signals. In this review, we discuss the latest studies that describe how various mechanical forces in the TME, including matrix stiffening, fluid shear stress, compressive forces, and interstitial fluid pressures, influence the mechanical phenotype of endothelial cells, including vascular integrity and angiogenesis. Additionally, we emphasize how these forces activate key mechanotransduction pathways, notably actin cytoskeletal reorganization through RhoA activation, downstream of FAK/Src and YAP/TAZ signaling, and remodel the tumor vasculature by increasing vascular permeability and neovascularization. Overall, we summarize the pivotal role of mechanotransduction in vascular barrier disruption and angiogenesis, providing new avenues for therapeutic strategies targeting tumor vasculature.