Our findings support a model wherein the silencing of miR‐335 in breast cancer cells enhances expression levels of PTPRN2 and PLCB1. PTPRN2 and PLCβ1 convergently reduce the levels of PI(4,5)P2 in the plasma membrane, dissociating cofilin from the membrane and enabling it to sever cytoplasmic actins to drive actin assembly, metastatic migration, and colonization (Fig 7A). Here, PTPRN2 is linked to breast cancer.