CD99 Drives Terminal Differentiation of Osteosarcoma Cells by Acting as a Spatial Regulator of ERK 1/2†

摘要: Differentiation therapy is an attractive treatment for osteosarcoma (OS). CD99 a cell surface molecule expressed in mesenchymal stem cells and osteoblasts that maintained during osteoblast differentiation while lost OS. Herein, we show whenever OS regain CD99, they become prone to reactivate the terminal program. In differentiating conditions, CD99-transfected express osteocyte markers, halt proliferation, largely die by apoptosis, resembling fate of mature osteoblasts. induces ERK activation, increasing its membrane-bound/cytoplasmic form rather than affecting nuclear localization. Through cytoplasmic ERK, promotes activity main osteogenic transcriptional factors AP1 RUNX2, which turn enhance osteocalcin p21WAF1/CIP1, leading G0/G1 arrest. These data underscore alternative positions active into distinct subcellular compartments as key events determining fate. © 2014 The Authors. Journal Bone Mineral Research published Wiley Periodicals, Inc. on behalf American Society Research.