黑素细胞
黑色素瘤
生物
干细胞
癌症研究
小眼畸形相关转录因子
肿瘤微环境
细胞生物学
免疫学
转录因子
基因
遗传学
肿瘤细胞
作者
Hong‐Seok Moon,Leanne R. Donahue,Eunju Choi,Philip O. Scumpia,William E. Lowry,Jennifer K. Grenier,Jerry Zhu,Andrew C. White
出处
期刊:Cell Stem Cell
[Elsevier]
日期:2017-10-13
卷期号:21 (5): 665-678.e6
被引量:108
标识
DOI:10.1016/j.stem.2017.09.001
摘要
Melanoma is one of the deadliest cancers, yet the cells of origin and mechanisms of tumor initiation remain unclear. The majority of melanomas emerge from clear skin without a precursor lesion, but it is unknown whether these melanomas can arise from melanocyte stem cells (MCSCs). Here we employ mouse models to define the role of MCSCs as melanoma cells of origin, demonstrate that MCSC quiescence acts as a tumor suppressor, and identify the extrinsic environmental and molecular factors required for the critical early steps of melanoma initiation. Specifically, melanomas originate from melanoma-competent MCSCs upon stimulation by UVB, which induces MCSC activation and translocation via an inflammation-dependent process. Moreover, the chromatin-remodeling factor Hmga2 in the skin plays a critical role in UVB-mediated melanomagenesis. These findings delineate melanoma formation from melanoma-competent MCSCs following extrinsic stimuli, and they suggest that abrogation of Hmga2 function in the microenvironment can suppress MCSC-originating cutaneous melanomas.
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