Runx2 expression: A mesenchymal stem marker for cancer

Abstract

Abstract. The transcription factor runt-related transcription factor 2 (Runx2) is a master gene implicated in the osteogenic differentiation of mesenchymal stem cells, and thus serves a determinant function in bone remodelling and skeletal integrity. Various signalling pathways regulate Runx2 abundance, which requires a number of molecules to finely modulate its expression. Furthermore, this gene may be ectopically-expressed in cancer cells. Recent studies have reported the involvement of Runx2 in cell proliferation, epithelial-mesenchymal transition, apoptosis and metastatic processes, suggesting it may represent a useful therapeutic target in cancer treatment. However, studies evaluating this gene as a cancer marker are lacking. In the present study, Runx2 expression was analysed in 11 different cancer cell lines not derived from bone tumour. In addition, the presence of Runx2-related cell-free RNA was examined in the peripheral blood of 41 patients affected by different forms of tumours. The results demonstrated high expression levels of Runx2 in the cancer cell lines and identified the presence of Runx2-related cell-free RNA in the peripheral blood of patients with cancer. As compared with normal individuals, the expression level was increased by 14.2-fold in patients with bone metastases and by 4.01-fold in patients without metastases. The results of the present study therefore opens up the possibility to exploit Runx2 expression as a cancer biomarker allowing the use of minimally invasive approaches for diagnosis and follow-up.

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

“…Its expression is high in pre-osteoblasts and in early osteoblasts, but decreases in mature osteoblasts [32]. However, RUNX2 is involved also in cellular transformation and appears upregulated in different solid tumors [9]. RUNX2 is ectopically expressed in melanoma and plays an important role in progression [7,8,33,34].…”

“…RUNX2 overexpression has been reported in breast cancer, pancreatic cancer, prostate cancer, lung cancer, ovarian epithelial cancer and melanoma. In previous studies, we identified RUNX2 as a stemness marker for cancer [9,10] and observed higher levels of RUNX2 expression in thyroid cancer patients with bone metastases [11]. RUNX2 appears to be involved in the osteolytic process [7,12].…”

Osteogenic Differentiation in Healthy and Pathological Conditions

“…Furthermore, the TGFβ and WNT pathways are known to induce oncogenic EMT and signaling pathways [ 39 ]. Recently, we reported that the osteogenic transcription factor RUNX2 may be considered a mesenchymal stem cell marker for cancer and that overexpression of this gene in solid tumors such as prostate, breast, pancreatic and lung cancer is associated with bone metastases [ 40 ]. Abnormal mesenchymal cell differentiation and overexpression of proto-oncogenes and downregulation of onco-suppressors are involved in the pathogenesis of osteosarcoma, a devastating bone tumor with a poor prognosis that affects children and adolescents.…”

BEL β-Trefoil Reduces the Migration Ability of RUNX2 Expressing Melanoma Cells in Xenotransplanted Zebrafish

“…In general, transcription factors may affect cellular processes and trigger cellular transformation. RUNX2, the master transcription factor for osteogenic differentiation, is overexpressed in several tumor tissues, including pancreatic cancer, breast cancer, ovarian epithelial cancer, prostate cancer, lung cancer, thyroid cancer and in osteosarcoma [14]. Lectins are biomolecules holding at least one non-catalytic domain able to bind specific monosaccharides or oligosaccharides [15].…”