Dataset Information

RUNX2 stimulates neoangiogenesis through the RUNT domain in melanoma

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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Publications

Runx2 stimulates neoangiogenesis through the Runt domain in melanoma.

Cecconi Daniela D Brandi Jessica J Manfredi Marcello M Serena Michela M Dalle Carbonare Luca L Deiana Michela M Cheri Samuele S Parolini Francesca F Gandini Alberto A Marchetto Giulia G Innamorati Giulio G Avanzi Francesco F Antoniazzi Franco F Marengo Emilio E Tiso Natascia N Mottes Monica M Zipeto Donato D Valenti Maria Teresa MT

Scientific reports 20190529 1

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 prot ...[more]

PMID: 31142788

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Project description:Gravitational biology and its effects on cancer cells are of great interest, especially today that space is more accessible than ever. Despite advances in space research, little is known about the impact of microgravity on tumor and its biology and data from the literature are often contradictory due to different setup, experimental designs and analyzed time-points. Exploiting the Random Positioning machine we evaluated on pancreatic cancer cells the effects of long-term exposure to simulated microgravity (SMG) performing a large proteomic, lipidomic and transcriptional analysis at 1, 7 and 9 days. Results indicate that SMG affects cellular morphology through a time-dependent activation of “Regulation of actin-based motility by Rho”and “Cdc42” pathways that contribute to the dynamic actin rearrangement involved in the formation of 3D spheroidal structures and in the enhancement of epithelial-to mesenchymal transition. To support energy stress remediation and counteract massive apoptosis activation and cell proliferation inhibition, induced by SMG, tumor cells downregulate the protein translational machinery, and undergo a metabolic reprogramming orchestrated by the activation of HIF-1a and PI3K/Akt pathways. These two pathways pave the way for glucose metabolism encouraging upregulation of glycolysis, mitochondrial activity, Tri-carboxylic acid cycle and fatty acid synthesis (rather than B oxidation), suggesting a de novo synthesis of triglycerides involved in the formation of membrane lipid bilayer and signaling mediators. This metabolic plasticity, typical of cancer stem cells, is in accordance with the SMG-mediated activation of PI3K/Akt/NFkB/ERK5/IL-8 signaling axis that significantly upregulates the expression of stem-associated proteins and expansion of cancer stem cells with a more mesenchymal phenotype and improved migratory capability. Altogether, our findings clearly indicate that microgravity induces cancer cell transformation towards the acquisition of cancer stem cell-like features, with a more aggressive and metastatic potential and pave the base for future study of response to anti neoplastic drugs under simulated microgravity.

Dataset Information

RUNX2 stimulates neoangiogenesis through the RUNT domain in melanoma

Publications

Runx2 stimulates neoangiogenesis through the Runt domain in melanoma.

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