TY - JOUR
T1 - CD99 drives terminal differentiation of osteosarcoma cells by acting as a spatial regulator of ERK 1/2
AU - Sciandra, Marika
AU - Marino, Maria Teresa
AU - Manara, Maria Cristina
AU - Guerzoni, Clara
AU - Grano, Maria
AU - Oranger, Angela
AU - Lucarelli, Enrico
AU - Lollini, Pier Luigi
AU - Dozza, Barbara
AU - Pratelli, Loredana
AU - Di Renzo, Maria Flavia
AU - Colombo, Mario Paolo
AU - Picci, Piero
AU - Scotlandi, Katia
PY - 2014/5
Y1 - 2014/5
N2 - Differentiation therapy is an attractive treatment for osteosarcoma (OS). CD99 is a cell surface molecule expressed in mesenchymal stem cells and osteoblasts that is maintained during osteoblast differentiation while lost in OS. Herein, we show that whenever OS cells regain CD99, they become prone to reactivate the terminal differentiation program. In differentiating conditions, CD99-transfected OS cells express osteocyte markers, halt proliferation, and largely die by apoptosis, resembling the fate of mature osteoblasts. CD99 induces ERK activation, increasing its membrane-bound/cytoplasmic form rather than affecting its nuclear localization. Through cytoplasmic ERK, CD99 promotes activity of the main osteogenic transcriptional factors AP1 and RUNX2, which in turn enhance osteocalcin and p21WAF1/CIP1, leading to G 0/G1 arrest. These data underscore the alternative positions of active ERK into distinct subcellular compartments as key events for determining OS fate.
AB - Differentiation therapy is an attractive treatment for osteosarcoma (OS). CD99 is a cell surface molecule expressed in mesenchymal stem cells and osteoblasts that is maintained during osteoblast differentiation while lost in OS. Herein, we show that whenever OS cells regain CD99, they become prone to reactivate the terminal differentiation program. In differentiating conditions, CD99-transfected OS cells express osteocyte markers, halt proliferation, and largely die by apoptosis, resembling the fate of mature osteoblasts. CD99 induces ERK activation, increasing its membrane-bound/cytoplasmic form rather than affecting its nuclear localization. Through cytoplasmic ERK, CD99 promotes activity of the main osteogenic transcriptional factors AP1 and RUNX2, which in turn enhance osteocalcin and p21WAF1/CIP1, leading to G 0/G1 arrest. These data underscore the alternative positions of active ERK into distinct subcellular compartments as key events for determining OS fate.
KW - CD99
KW - RUNX2
KW - mapk signaling
KW - osteoblast differentiation
KW - osteosarcoma
UR - http://www.scopus.com/inward/record.url?scp=84899092275&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899092275&partnerID=8YFLogxK
U2 - 10.1002/jbmr.2141
DO - 10.1002/jbmr.2141
M3 - Article
C2 - 24677094
AN - SCOPUS:84899092275
SN - 0884-0431
VL - 29
SP - 1295
EP - 1309
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
IS - 5
ER -