We establish that kindlin-3 phosphorylation is crucial for kindlin-3 function in BC as supported by the following findings: kindlin-3 induced spreading and invasion in vitro and tumor progression, and metastasis in mice in vivo is blunted in T482S484/AA kindlin-3 cells; kindlin-3 induced tumor angiogenesis, and macrophage recruitment is inhibited in T482S484/AA kindlin-3 cells; Twist expression was significantly blunted in vitro and in tumors derived T482S484/AA kindlin-3–expressing cells; kindlin-3–mediated regulation of the EMT program in BC depends on kindlin-3 phosphorylation. Here, TWIST1 is linked to breast cancer.