Regulated turnover of integrin receptors is essential for cell adhesion and 
migration. Pathways selectively regulating β1-integrin recycling are implicated 
in cancer invasion and metastasis, yet proteins required for the internalization 
of this pro-invasive integrin remain to be identified. Here, we uncover 
formin-like 2 (FMNL2) as a critical regulator of β1-integrin internalization 
downstream of protein kinase C (PKC). PKCα associates with and phosphorylates 
FMNL2 at S1072 within its Diaphanous autoregulatory region, leading to the 
release of formin autoinhibition. Phosphorylation of FMNL2 triggers its rapid 
relocation and promotes its interaction with the cytoplasmic tails of the 
α-integrin subunits for β1-integrin endocytosis. FMNL2 drives β1-integrin 
internalization and invasive motility in a phosphorylation-dependent manner, 
while a FMNL2 mutant defective in actin assembly interferes with β1-integrin 
endocytosis and cancer cell invasion. Our data establish a role for FMNL2 in the 
regulation of β1-integrin and provide a mechanistic understanding of the 
function of FMNL2 in cancer invasiveness.