Figure 9.

TRPC5 drives filopodia formation by activating the ATP/p-MLC/p-Cortactin signaling axis. Activation of TRPC5 channels in gastrointestinal cancer cells triggers calcium ion influx, leading to the formation of the Ca²⁺-CaM complex, which promotes ATP-dependent MLC phosphorylation. This phosphorylation enhances the activation and localization of cortactin at the filopodia tips, regulating their formation and stabilization. Kaempferol, a promising natural small-molecule TRPC5 inhibitor, disrupts this process by targeting TRPC5, thereby inhibiting filopodia formation and stabilization, ultimately suppressing the metastasis of gastrointestinal cancer.