A novel function of “inactive” cytoplasmic ezrin in its closed conformation as an RNA binding protein to mediate osteosarcoma metastasis

Phosphorylation at the threonine 567 residue confers an open form on ezrin by removing the head-to-tail interaction. Open ezrin was generally accepted as the active form because it can translocate to the plasma membrane and link the actin cytoskeleton to the membrane proteins.

Closed ezrin, sequestered in the cytoplasm was considered inactive. Our previous work established that ezrin directly interacts with RNA binding proteins (RBPs), and here we show that ezrin expression correlates with cytoplasmic RBPs in human osteosarcoma samples. Therefore, we hypothesized that closed ezrin is not a dormant protein, but rather biologically active.