小眼畸形相关转录因子
黑色素瘤
转移
癌症研究
转录组
肿瘤微环境
生物
医学
癌症
内科学
肿瘤细胞
转录因子
基因
基因表达
遗传学
作者
Chuan‐Yuan Wei,Wei Sun,Kangjie Shen,Jingqin Zhong,Wanlin Liu,Zixu Gao,Yu Xu,Lu Wang,Tu Hu,Mingchun Ren,Yinlam Li,Yuanyuan Zhu,Shaoluan Zheng,Man Zhu,Rongkui Luo,Yanwen Yang,Yingyong Hou,Qi Feng,Yuhong Zhou,Yong Chen,Jiande Gu
标识
DOI:10.1038/s41467-023-43980-y
摘要
Abstract Acral melanoma (AM) is a rare subtype of melanoma characterized by a high incidence of lymph node (LN) metastasis, a critical factor in tumor dissemination and therapeutic decision-making. Here, we employ single-cell and spatial transcriptomic analyses to investigate the dynamic evolution of early AM dissemination. Our findings reveal substantial inter- and intra-tumor heterogeneity in AM, alongside a highly immunosuppressive tumor microenvironment and complex intercellular communication networks, particularly in patients with LN metastasis. Notably, we identify a strong association between MYC + Melanoma ( MYC + MEL) and FGFBP2 + NKT cells with LN metastasis. Furthermore, we demonstrate that LN metastasis requires a metabolic shift towards fatty acid oxidation (FAO) induced by MITF in MYC + MEL cells. Etomoxir, a clinically approved FAO inhibitor, can effectively suppress MITF-mediated LN metastasis. This comprehensive dataset enhances our understanding of LN metastasis in AM, and provides insights into the potential therapeutic targeting for the management of early AM dissemination.
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