癌症研究
细胞生物学
黑色素瘤
转录因子
激活剂(遗传学)
生物
STAT蛋白
抄写(语言学)
细胞生长
磷酸化
车站3
医学
内科学
基因
受体
哲学
生物化学
遗传学
语言学
作者
Henri Montaudié,Laura Sormani,Bérengère Dadone-Montaudié,Marjorie Heim,Nathalie Cardot-Leccia,Meri K. Tulic,Guillaume E. Beranger,Delphine Debayle,Yann Cheli,Jérémy H. Raymond,Pierre Sohier,Valérie Petit,Stéphane Rocchi,Franck Gesbert,Lionel Larue,Thierry Passeron
标识
DOI:10.1016/j.jid.2021.05.035
摘要
The potential role of CLEC12B, a gene predominantly expressed by skin melanocytes discovered through transcriptomic analysis, in melanoma is unknown. In this study, we show that CLEC12B expression is lower in melanoma and melanoma metastases than in melanocytes and benign melanocytic lesions and that its decrease correlates with poor prognosis. We further show that CLEC12B recruits SHP2 phosphatase through its immunoreceptor tyrosine-based inhibition motif domain, inactivates signal transducer and activator of transcription 1/3/5, increases p53/p21/p27 expression/activity, and modulates melanoma cell proliferation. The growth of human melanoma cells overexpressing CLEC12B in nude mice after subcutaneous injection is significantly decreased compared with that in the vehicle control group and is associated with decreased signal transducer and activator of transcription 3 phosphorylation and increased p53 levels in the tumors. Reducing the level of CLEC12B had the opposite effect. We show that CLEC12B represses the activation of the signal transducer and activator of transcription pathway and negatively regulates the cell cycle, providing a proliferative asset to melanoma cells.
科研通智能强力驱动
Strongly Powered by AbleSci AI