Ectopic expression of the osteogenic master gene RUNX2 in melanoma.

The transcription factor RUNX2 is the osteogenic master gene expressed in mesenchymal stem cells during osteogenic commitment as well as in pre-osteoblasts and early osteoblasts. However, RUNX2 is also ectopically expressed in melanoma and other cancers. Malignant melanoma (MM) is a highly metastatic skin cancer. The incidence of MM has increased considerably in the past half-century. The expression levels and mutation rates of genes such as BRAF , KIT , NRAS , PTEN , P53 , TERT and MITF are higher in melanoma than in other solid malignancies. Additionally, transcription factors can affect cellular processes and induce cellular transformation since they control gene expression. Recently, several studies have identified alterations in RUNX2 expression. In particular, the regulation of KIT by RUNX2 and the increased expression of RUNX2 in melanoma specimens have been shown. Melanocytes, whose transformation results in melanoma, arise from the neural crest and therefore show "stemness" features. RUNX2 plays an important role in the re-activation of the MAPK and PI3K/AKT pathways, thus endowing melanoma cells with a high metastatic potential. In melanoma, the most frequent metastatic sites are the lung, liver, brain and lymph nodes. In addition, bone metastatic melanoma has been described. Notably, studies focusing on RUNX2 may contribute to the identification of an appropriate oncotarget in melanoma.