Delineating the early dissemination mechanisms of acral melanoma by integrating single-cell and spatial transcriptomic analyses.
Chuanyuan WeiWei SunKangjie ShenJingqin ZhongWanlin LiuZixu GaoYu XuLu WangTu HuMing RenYinlam LiYu ZhuShaoluan ZhengMing ZhuRong-Kui LuoYanwen YangYing-Yong HouFazhi QiYuhong ZhouYong ChenJianying GuPublished in: Nature communications (2023)
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.