RUNX2 Transcriptional Regulation in Development and Disease

Abstract

RUNX2, a member of the Runt family of transcription factors, plays important roles in embryonic development to promote osteogenesis and angiogenesis. RUNX2 has been implicated in the promotion of disease, including cleidocranial dysplasia, in cancer progression, and in metastasis of breast and prostate tumors. Its aberrant expression in disease states may be the result of several mechanisms such as haploinsufficiency, mutation, or amplification. In osteogenesis and cancer progression, interactions with core-binding factor-β (Cbf-β) and other cofactors are responsible for the regulation of target gene expression including, but not limited to, VEGF, osteopontin, osteocalcin, MMPs, and BMPs. RUNX2 transcriptional function within cells is regulated by signal transduction events leading to activation of ERK, Smads, cdks, and Akt, which result in phosphorylation, DNA binding, and transcriptional activation or repression of target genes. Constitutive activation of signaling pathways in tumor cells results in aberrant expression and activation of RUNX2. Specific RUNX2 targeting agents, therefore, may bypass the effects of redundant signal transduction pathways within cancer cells and be an effective therapeutic strategy for treatment of RUNX2-positive cancer patients. © Springer Science+Business Media New York 2014.