Epigenetically regulated PCDHB15 impairs aggressiveness of metastatic melanoma cells - Archive ouverte HAL Access content directly
Journal Articles Clinical Epigenetics Year : 2022

Epigenetically regulated PCDHB15 impairs aggressiveness of metastatic melanoma cells

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Abstract

The protocadherin proteins are cell adhesion molecules at the crossroad of signaling pathways playing a major role in neuronal development. It is now understood that their role as signaling hubs is not only important for the normal physiology of cells but also for the regulation of hallmarks of cancerogenesis. Importantly, protocadherins form a cluster of genes that are regulated by DNA methylation. We have identified for the first time that PCDHB15 gene is DNA-hypermethylated on its unique exon in the metastatic melanoma-derived cell lines and patients’ metastases compared to primary tumors. This DNA hypermethylation silences the gene, and treatment with the DNA demethylating agent 5-aza-2′-deoxycytidine reinduces its expression. We explored the role of PCDHB15 in melanoma aggressiveness and showed that overexpression impairs invasiveness and aggregation of metastatic melanoma cells in vitro and formation of lung metastasis in vivo. These findings highlight important modifications of the methylation of the PCDHβ genes in melanoma and support a functional role of PCDHB15 silencing in melanoma aggressiveness.
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Origin : Publication funded by an institution
Licence : CC BY - Attribution

Dates and versions

pasteur-03946850 , version 1 (19-01-2023)
pasteur-03946850 , version 2 (20-01-2023)

Licence

Attribution - CC BY 4.0

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Arnaud Carrier, Cécile Desjobert, Valérie Lobjois, Lise Rigal, Florence Busato, et al.. Epigenetically regulated PCDHB15 impairs aggressiveness of metastatic melanoma cells. Clinical Epigenetics, 2022, 14 (1), pp.156. ⟨10.1186/s13148-022-01364-x⟩. ⟨pasteur-03946850v2⟩
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