Figure 3.

TRP- small GTPases signaling pathways interplay in aberrant tumor vascularization. Cartoon depicting TRP channels signaling pathways affecting tumor vascularization through GTPases. TRPV4 induces aberrant mechano-sensivity to ECM through the Ca²⁺-dependent inhibition of Rho/ROCK pathway; TRPC1 and TRPC6 enhance vessels permeability affecting cell contractility through a Ca²⁺-mediated regulation of RhoA; on the contrary, TRPM8 exerts a protective role in tumor vasculature permeability, inhibiting the store-operated RhoA activation and subsequent cell contraction; TRPM8 also inhibits ECs adhesion and migration, impairing activation of β₁-integrin through the intracellular retention of Rap1. VE-cadherin, vascular E-cadherin; FAK, focal adhesion kinase; ROCK, Rho-associated protein kinase; MLC, myosin light chain; PKCα, protein kinase C alpha; IP3R, inositol trisphosphate receptor; PAR-1, protease-activated receptor-1.