Cutaneous melanoma is a very aggressive tumour as it can metastasise efficiently. Despite the development of targeted therapies and immunotherapy, melanoma remains the most serious form of skin cancer. Different signalling pathways have been implicated in tumorigenesis. In particular, the β-catenin signalling pathway plays a key role in many cellular functions and is commonly deregulated in cancers, including melanoma. Activation of β-catenin signalling occurs in deep nevi and melanoma due to specific mutations in CTNNB1 (the gene encoding β-catenin) and APC, as well as to allogenetic modifications associated with this pathway. Here, our goal was to discover new effectors to better understand the functions of β-catenin. To this end, we used a bioinformatics approach to compare human melanomas with β-catenin-activating genomic events (mutations in CTNNB1 and APC) to control melanomas using data from 368 melanoma samples from the Cancer Genome Atlas (TCGA) Skin Melanoma Study. Using the information from the RNA-Seq, we identified a target gene signature of 339 genes (238 genes are up-regulated and 101 are down-regulated), some of which are known and some of which were not. From this study, we can conclude that activation of the β-catenin signalling pathway is associated with poorer overall survival in melanoma - a question still debated in the literature. Specifically, we showed that the level of XC53A, UBM3 and BXIT19 were strongly induced and validated in vitro, that these genes were indeed regulated by β-catenin in several melanoma cell lines, and that they could affect cell proliferation and migration. In conclusion, we identified and validated three new targets of β-catenin affecting proliferation and migration; two fundamental cellular mechanisms involved in melanomagenesis.

ESDR284 - Emergence of new β-catenin effectors with a function in melanomagenesis

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING