Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jul 26, 2018; 10(7): 78-81
Published online Jul 26, 2018. doi: 10.4252/wjsc.v10.i7.78
Ectopic expression of the osteogenic master gene RUNX2 in melanoma Maria Teresa Valenti, Luca Dalle Carbonare, Monica Mottes
Maria Teresa Valenti, Luca Dalle Carbonare, Monica Mottes
Maria Teresa Valenti, Luca Dalle Carbonare, Department of Medicine, University of Verona, Verona 37100, Italy
Monica Mottes, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona 37100, Italy
Author contributions: Valenti MT and Mottes M conceived the study; Valenti MT, Dalle Carbonare L and Mottes M drafted the manuscript; all authors approved the final version of the paper.
Conflict-of-interest statement: The authors have no conflict of interest to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Maria Teresa Valenti, BSc, PhD, Chief Technician, Research Fellow, Department of Medicine, University of Verona, Ple Scuro 10, Verona 37100, Italy. mariateresa.valenti@univr.it
Telephone: +39-45-8128450
Received: May 23, 2018
Peer-review started: May 25, 2018
First decision: June 5, 2018
Revised: June 11, 2018
Accepted: June 28, 2018
Article in press: June 28, 2018
Published online: July 26, 2018

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.

Keywords: RUNX2, Mesenchymal stem cells, Epitelial mesenchymal transition, Bone, Melanoma

Core tip: In addition to its physiological expression in osteogenic cells, RUNX2 ectopic expression is also reported in several cancers. Melanoma cells, which arise from the neural crest, are not typical epithelial cells and exhibit “stemness” features. For this reason the epithelial mesenchymal transition process may be enhanced in melanoma cells. RUNX2 expression in such context increases the migration and invasiveness of melanoma cells; it can therefore be considered a new oncotarget in melanoma.