TY - JOUR T1 - CD47 Activation-induced UHRF1 Over-expression Is Associated with Silencing of Tumor Suppressor Gene <em>p16<sup>INK4A</sup></em> in Glioblastoma Cells JF - Anticancer Research JO - Anticancer Res SP - 149 LP - 157 VL - 35 IS - 1 AU - ABDELAZIZ BOUKHARI AU - MAHMOUD ALHOSIN AU - CHRISTIAN BRONNER AU - KRIZIA SAGINI AU - CÉCILE TRUCHOT AU - EMILIE SICK AU - VALERIE B. SCHINI-KERTH AU - PHILIPPE ANDRÉ AU - YVES MÉLY AU - MARC MOUSLI AU - JEAN-PIERRE GIES Y1 - 2015/01/01 UR - http://ar.iiarjournals.org/content/35/1/149.abstract N2 - CD47, an integrin-associated protein is over-expressed in several tumors including glioblastomas. Activation of CD47 induces proliferation of human astrocytoma cells but not normal astrocytes via an Akt-dependent way. However, the pathways mediating this process are still unknown. The epigenetic integrator UHRF1 (Ubiquitin-like containing PHD and RING Finger 1) is over-expressed in various cancers and plays a vital role in the silencing of numerous tumor suppressor genes including p16INK4A, thereby promoting cell proliferation. The aim of the present study was to investigate the role of UHRF1 and p16INK4A in CD47-induced effects. Herein we showed that activation of CD47 in human astrocytoma cell lines U87 and CCF- STTG1 (Grade IV), up-regulated the expression of UHRF1 with subsequent down-regulation of p16INK4A, thus promoting cell proliferation. Blockage of CD47 using a blocking antibody down-regulated UHRF1 expression, accompanied by a re-expression of p16INK4A, conducting to decreased cell proliferation in both cancer cell lines. Neither CD47 activation nor its blocking has any effect on UHRF1/p16INK4A expression in normal human astrocytes. Depletion of CD47 in the U87 cell line resulted in down-regulation of UHRF1. We also found that CD47 activated the inflammatory genes IL-6, IL-7 and MCP-1 by a NF-κB-dependent mechanism in human astrocytoma but not in normal astrocytes. In conclusion, the present findings indicate that CD47 activation increases expression of UHRF1 and suggest, for the first time, that CD47 regulates the epigenetic code by targeting UHRF1. This could represent a new pathway towards cell proliferation and metastasis. ER -