Abstract
Runx2 is a transcription factor involved in melanoma cell migration and proliferation. Here, we extended the analysis of Runt domain of Runx2 in melanoma cells to deepen understanding of the underlying mechanisms. By the CRISPR/Cas9 system we generated the Runt KO melanoma cells 3G8. Interestingly, the proteome analysis showed a specific protein signature of 3G8 cells related to apoptosis and migration, and pointed out the involvement of Runt domain in the neoangiogenesis process. Among the proteins implicated in angiogenesis we identified fatty acid synthase, chloride intracellular channel protein-4, heat shock protein beta-1, Rho guanine nucleotide exchange factor 1, D-3-phosphoglycerate dehydrogenase, myosin-1c and caveolin-1. Upon querying the TCGA provisional database for melanoma, the genes related to these proteins were found altered in 51.36% of total patients. In addition, VEGF gene expression was reduced in 3G8 as compared to A375 cells; and HUVEC co-cultured with 3G8 cells expressed lower levels of CD105 and CD31 neoangiogenetic markers. Furthermore, the tube formation assay revealed down-regulation of capillary-like structures in HUVEC co-cultured with 3G8 in comparison to those with A375 cells. These findings provide new insight into Runx2 molecular details which can be crucial to possibly propose it as an oncotarget of melanoma.
Highlights
Runx[2] is a transcription factor involved in melanoma cell migration and proliferation
We identified for the first time proteins associated with the Runt domain involved in promoting migration, proliferation and in particular in neoangiogenesis of melanoma cells
Our previous study showed that Runt domain KO melanoma cells are characterized by reduced proliferation, epithelial-mesenchymal transition and metastasis, suggesting that the Runt domain of Runx[2] may represent an oncotarget in melanoma[11]
Summary
Runx[2] is a transcription factor involved in melanoma cell migration and proliferation. In order to identify the molecular pathways associated with RUNX2 in melanoma we performed a comparative shotgun proteomic analysis of Runt KO (3G8) and wild-type (A375) melanoma cells.
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