Cortactin recruits FMNL2 to promote actin polymerization and endosome motility in invadopodia formation

Abstract Recently, invadopodiahave been increasingly recognized as important drivers of local invasion and metastasis. Cortactin, as an actin-binding protein, is closely associated with invadopodiathrough interacting with proteins. Formin-like 2 (FMNL2), a member of diaphanous-related forminswhich act as nucleation factors, plays an important role in tumor progression. But whether cortactincan interact with FMNL2 to promote invadopodiaformation and the role of FMNL2 in invadopodiaformation are still unknown. Here we found that cortactindirectly bound to FMNL2 and elevated the activities of actin polymerization and recycling endosome motility. FMNL2 was necessary for invadopodiaformation and function in CRC cells. The interaction of cortactinand FMNL2 could further promote the invadopodiaformation and matrix degradation. The stimulation of EGF/ cdc42enhanced the combination of cortactinand FMNL2 to intensify the numbers of invadopodiaand the degrees of matrix degradation. In vivo, induction of invadopodiaformation via cortactinis essential for the ability of FMNL2 to promote CRC metastasis. Furthermore, up-regulations of FMNL2 and cortactinwere highly linked in CRC tissues. Collectively, our work demonstrates a brand-new mechanism of cortacin and FMNL2 at invadopodiain CRC.