SHP-2 and the JAK/STAT pathway are demonstrated to have a major impact in melanoma. Here, we demonstrated that the expression of CLEC12B, a melanocytic gene that we have uncovered using transcriptome analysis, is decreased in melanoma cells and melanoma metastases compared to benign melanocytic lesions, and this decreased expression in tumors is correlated to a poor prognosis. Up to now, no data concerning CLEC12B and melanoma was published CLEC12B. CLEC12B recruits SHP-2 through its ITIM domain and downstream inactivates STAT-1, 3 and 5 and increases p53/p21/p27 expression. Thus, the overexpression of CLEC12B leads to a slowdown in G0-G1 phase of cell cycle and inhibits melanoma proliferation in vitro, while opposite effects are observed after its silencing. Melanoma cells over-expressing CLEC12B were used in tumor xenograft experiments and showed a significant decrease of tumor growth and of phosphorylation of STAT3 with a concomitant increase of p53 within the tumors, and opposite effect when it is silenced. Our findings reveal CLEC12B as a novel potent suppressor gene in melanoma by regulating cell cycle and repressing STAT activation.

CLEC12B a new gene implicated in melanoma