Oncogenic BRAF noncanonically promotes tumor metastasis by mediating VASP phosphorylation and filopodia formation

The study uncovered a distinct mechanism. BRAF, particularly the BRAFV600E mutation, was found to induce the formation of invasive cancer cell filopodia at the plasma membrane. It achieved this by physically interacting with Vasodilator-stimulated phosphoprotein (VASP) and catalyzing VASP phosphorylation at Ser157. Inhibiting VASP or Ser157 phosphorylation reduced motility, invasion, and metastasis in BRAF or KRAS mutant tumor cells. Clinical data also showed a correlation between BRAFV600E expression and invasion, emphasizing VASP Ser157 phosphorylation as a potential therapeutic target in these cancers.