Pharmacological manipulation of TRPC5 by kaempferol attenuates metastasis of gastrointestinal cancer via inhibiting calcium involved in the formation of filopodia

The thermo-sensory receptor, transient receptor potential channel 5 (TRPC5), a non-selective calcium ion (Ca²⁺)-permeable ion channel, has been implicated in cancer initiation and progression. However, its specific role in gastrointestinal cancer remains unclear. This study demonstrates that TRPC5 is significantly overexpressed in gastrointestinal tumors and is inversely associated with patient prognosis. TRPC5 overexpression triggers a substantial elevation in intracellular Ca²⁺ levels ([Ca²⁺]i), driving actin cytoskeleton reorganization and facilitating filopodia formation. Furthermore, kaempferol, a compound sourced from traditional Chinese medicine, is identified as a TRPC5 inhibitor that effectively suppresses its activity, thereby impeding gastrointestinal cancer metastasis. These findings underscore the potential of TRPC5 as a therapeutic target for metastasis inhibition, with kaempferol emerging as a promising natural inhibitor that could be optimized for clinical use in preventing cancer metastasis.