In-depth characterization of the functional signaling at play shows that Breast Cancer Anti-estrogen Resistance 3 (BCAR3) is a genuine new SMYD2 substrate and that its mono-methylation at lysine 334 (K334me1) acts as a docking site for a new family of methyl-binding proteins, the Formin-Like proteins (FMNLs16). Here, BCAR3 is linked to cancer.