478 MICAL2, upregulated by β-catenin, induces invasion in melanoma

The Wnt/β-catenin signaling pathway plays a key role during embryonic development, homeostasis and cancer. The role of β-catenin in melanocyte lineage establishment and homeostasis has been elucidated, but its role in melanoma remains poorly defined. In particular, its function in cell invasion is controversial. Especially, we generated a signature of β-catenin activation to emerge proteins of interest including known β-catenin target genes (AXIN2, APCDD1, NKD1, SP5, NOTUM, ZNRF3, CCND1 and PPARD) and new genes (SLC1A5, SLC7A11, SLC24A4 and MICAL2). Our signature gene most correlated with invasive cells is MICAL2. MICAL2 oxidizes actin filaments, destabilizes them, and modifies the migratory power of cells. In melanoma cell lines, reduction or induction reduces or increases the level of MICAL2, respectively. Decreasing the level of MICAL2 reduces migration, invasion and cell growth. Finally, a significantly unfavorable evolution for the patient is associated with a strong expression of MICAL2 and its invasive power. In conclusion, the identification of a transcriptional signature of β-catenin activation in melanoma is an important step towards understanding the role of β-catenin during melanomagenesis. MICAL2 which is pharmacologically targetable is an example.