Exploring the Interplay of RUNX2 and CXCR4 in Melanoma Progression.

Overexpression of the Runt-related transcription factor 2 () has been reported in several cancer types, and the C-X-C motif chemokine receptor 4 () has an important role in tumour progression. However, the interplay between and in melanoma cells remains poorly understood. In the present study, we used melanoma cells and a knockout (-KO) in vitro model to assess the influence of on CXCR4 protein levels along with its effects on markers associated with cell invasion and autophagy. Osteotropism was assessed using a 3D microfluidic model. Moreover, we assessed the impact of CXCR4 on the cellular levels of key cellular signalling proteins involved in autophagy. We observed that melanoma cells express both and . Restored expression in KO cells increased the expression levels of and proteins associated with the metastatic process. The protein markers of autophagy LC3 and beclin were upregulated in response to increased levels. The CXCR4 inhibitor WZ811 reduced osteotropism and activated the mTOR and p70-S6 cell signalling proteins. Our data indicate that the RUNX2 transcription factor promotes the expression of the CXCR4 chemokine receptor on melanoma cells, which in turn promotes autophagy, cell invasiveness, and osteotropism, through the inhibition of the mTOR signalling pathway. Our data suggest that promotes melanoma progression by upregulating , and we identify the latter as a key player in melanoma-related osteotropism.