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.

Cutaneous photoaging is associated with dermal elastic fiber remodeling; daily photoprotection is therefore essential to prevent ultraviolet (UV)-induced skin damage. Green tea (C sinensis), rich in polyphenol catechins (GTC), have been reported to have significant skin benefits in vitro and in vivo. We have performed a double-blind randomised controlled trial to assess whether systemic GTC supplementation can protect dermal elastic fibers from acute UV exposure. Healthy white Caucasians (n=50; 18-65 years) were randomized (1:1) to 12 weeks daily oral supplement (1080mg GTC with 100mg viatmin C) or placebo (maltodextrin). Biopsies were taken from skin exposed to 3xMED of solar simulated radiation (SSR) and unexposed skin at baseline and post-supplementation; compliance was confirmed by urinary GTC metabolite analysis. Dermal elastic fibers were identified via histology and immunohistochemistry, their distribution assessed in the papillary dermis (from the dermal-epidermal junction to a depth of 100μm) by image analysis. Differences between UV-exposed and unexposed skin were analysed by paired t-test. A total of 44 subjects completed the study, being compliant with supplementation and providing all skin samples. At baseline, SSR induced a significant overall loss of elastic fiber components (P= 0.001), and specifically fibulins-2 and -5. Post-supplementation, UV-mediated loss of fibulin-5 remained significant in the placebo group with mean (SD) % fiber area 19.4 (3.8) and 17.7 (4.1) in unexposed and UV-exposed skin resectively (P=0.01), whilst in the active group fibulin-5 was protected with % fiber area 18.1 (4.0) and 17.1 (2.7) in unexposed and UV-exposed skin respectively (P= 0.30). Hence, acute SSR exposure results in elastic fiber remodeling similar to that observed in chronically photoaged skin. Furthermore, in a randomized control trial, dietary GTC protected fibulin-5 microfibrils in the papillary dermis from UV-mediated degradation.