Histone Deacetylase Inhibitors Repress Tumoral Expression of the Proinvasive Factor RUNX2

Abstract

Aberrant reactivation of embryonic pathways occurs commonly in cancer. The transcription factor RUNX2 plays a fundamental role during embryogenesis and is aberrantly reactivated during progression and metastasization of different types of human tumors. In this study, we attempted to dissect the molecular mechanisms governing RUNX2 expression and its aberrant reactivation. We identified a new regulatory enhancer element, located within the RUNX2 gene, which is responsible for the activation of the RUNX2 promoter and for the regulation of its expression in cancer cells. Furthermore, we have shown that treatment with the anticancer compounds histone deacetylase inhibitor (HDACi) results in a profound inhibition of RUNX2 expression, which is determined by the disruption of the transcription-activating complex on the identified enhancer. These data envisage a possible targeting strategy to counteract the oncongenic function of RUNX2 in cancer cells and provide evidence that the cytotoxic activity of HDACi in cancer is not only dependent on the reactivation of silenced oncosuppressors but also on the repression of oncogenic factors that are necessary for survival and progression.Cancer Res; 75(9); 1868-82. Ó2015 AACR.

Role of CBX4 in the Colorectal Carcinoma Metastasis—Response

“…In fact, we also tried to detect the mRNA of RUNX2 isoform-II by qPCR assay, but the specificity for this primer was too low, as this primer melt curve showed two peaks, although the primers we used for detecting the RUNX2 isoform-I and isoform-II were the same ones designed by Sancisi and colleagues. These results indicate that the transcription of RUNX2 is complicated in cancer cells and support that additional regulatory elements, such as alternative promoters and enhancers (4), may also play crucial roles in controlling RUNX2 at multiple levels.…”

A Potential Role of RUNX2- RUNT Domain in Modulating the Expression of Genes Involved in Bone Metastases: An In Vitro Study with Melanoma Cells

“…In lung cancers, RUNX2 overexpression was shown to promote EMT via direct regulation of vimentin along with other proteins [36,37]. Recently, it was demonstrated that RUNX2 participates in the transcriptional regulation of vimentin [38].…”

Thyroid Hormone Receptor-β (TRβ) Mediates Runt-Related Transcription Factor 2 (Runx2) Expression in Thyroid Cancer Cells: A Novel Signaling Pathway in Thyroid Cancer

“…This observation is consistent with an activation of Runx2 mediated through this sequence. The Runx2-P1 promoter is characterized by repression and activation regions (56,61,62), as well as distinct regulatory DNA motifs and their cognate transcription factors (54 -56, 63, 64). Given the proximity of regulatory elements within this region near the TRE, it is possible that the mutation in TRE-A may alter additional nuclear protein complexes (56).…”