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A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
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Runx2 stimulates neoangiogenesis through the Runt domain in melanoma

Daniela Cecconi1, Jessica Brandi1, Marcello Manfredi2

  • 1Department of Biotechnology, Mass Spectrometry & Proteomics Lab, University of Verona, Verona, Italy.

Scientific Reports
|May 31, 2019
PubMed

Insights

Runx2

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Runx2 is a transcription factor influencing melanoma cell migration and proliferation.
  • Understanding the Runt domain of Runx2 in melanoma is crucial for mechanism elucidation.

Purpose of the Study:

  • To investigate the role of the Runx2 Runt domain in melanoma.
  • To identify molecular mechanisms underlying Runx2's function in melanoma.

Main Methods:

  • CRISPR/Cas9 gene editing to create Runt knockout (KO) melanoma cells (3G8).
  • Proteome analysis of 3G8 cells.
  • TCGA database query for gene alterations.
  • VEGF gene expression analysis.
  • Co-culture assays with HUVECs (Human Umbilical Vein Endothelial Cells).
  • Tube formation assay.

Main Results:

  • Proteome analysis revealed a distinct protein signature in 3G8 cells linked to apoptosis and migration.
  • The Runx2 Runt domain is implicated in neoangiogenesis.
  • Genes related to identified angiogenesis proteins are altered in 51.36% of melanoma patients in TCGA.
  • VEGF expression was reduced in 3G8 cells compared to A375 cells.
  • HUVECs co-cultured with 3G8 cells showed reduced expression of neoangiogenetic markers (CD105, CD31).
  • Tube formation assay demonstrated decreased capillary-like structures when HUVECs were co-cultured with 3G8 cells.

Conclusions:

  • The Runx2 Runt domain plays a significant role in melanoma neoangiogenesis.
  • Runx2 may be a potential oncotarget for melanoma treatment.
  • These findings offer novel molecular insights into Runx2's function in melanoma.

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