Role of RUNX2 in Melanoma: A New Player in Tumor Progression and Resistance to Therapy

Abstract

RUNX2, a transcription factor, initially known for its indispensable role in skeletal development. RUNX2 is essential for osteoblast differentiation and the maintain of the osteocyte balance. RUNX2 acts directly on osteoblasts via Fgf pathway or on mesenchymal progenitors through Hedgehog, Wnt, Pthlh and DLX5. Currently, many reports point its critical role in the progression and metastasis of several cancer types. RUNX2 is involved in EMT process, invasion and metastasis through the modulation of important oncogenic pathways, including Wnt, FAK/PTK and AKT. In melanoma, RUNX2 is a key player in mediating intrinsic RTK-associated pro-oncogenic properties. We have showed a dramatic up regulation of RUNX2 expression with concomitant up-regulation of EGFR, IGF-1R and AXL, in melanoma cells rendered resistant to BRAF mutant inhibitors. Approximately half of melanomas carry BRAF mutations which enhance tumor invasion and metastasis. In this chapter, we describe the potential mechanisms, leading to the upregulation of RUNX2 in melanoma with BRAF mutations. We also highlight the critical role of PI3K/AKT in the expression and activation of RUNX2, and its consequences on the regulation of many critical factors, controlling cancer invasion and metastasis.

Exploring the Interplay of RUNX2 and CXCR4 in Melanoma Progression

“…RUNX2, a transcription factor related to osteogenesis, has been identified as an important protein involved in melanoma progression [ 1 , 2 , 3 , 4 ]. Recent studies have shown that RUNX2 expression was upregulated in advanced melanomas and correlated with poor patient prognosis [ 5 , 6 ]. RUNX2 promotes cell adhesion, invasion, and metastasis through the activation of target genes involved in extracellular matrix degradation.…”