RUNX2 stimulates neoangiogenesis through the RUNT domain in melanoma
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ABSTRACT: Transcription factors, by acting on gene expression can affect molecular pathways and can thereby induce malignant transformation. Among the transcription factors involved in cellular transformation, we recently highlighted the role of RUNX2 in melanoma cell migration and proliferation. In the present study, we extended the analysis of the molecular effects 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. Therefore, using a proteomic approach, we compared 3G8 with the original wild-type melanoma cell line (A375). The results showed a specific protein signature of 3G8 cells related to apoptosis and migration. In addition, proteomic analysis allowed us to point out the involvement of the RUNT domain in the neoangiogenesis process. Among the deregulated proteins implicated in angiogenesis we found 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. Accordingly, the VEGF gene expression was higher in A375 compared to 3G8 cells; HUVEC cells expressed increased levels of the neoangiogenetic markers CD105 and CD31 when co-cultured with A375 cells. In conclusion, our study provided new insight into RUNX2 molecular details which can be crucial to possibly propose it as an oncotarget of melanoma.
INSTRUMENT(S): TripleTOF 5600
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Cell Culture
SUBMITTER: Marcello Manfredi
LAB HEAD: Marcello Manfredi
PROVIDER: PXD012096 | Pride | 2019-11-13
REPOSITORIES: Pride
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