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Delineating the early dissemination mechanisms of acral melanoma by integrating single-cell and spatial transcriptomic analyses

Author

Listed:
  • Chuanyuan Wei

    (Fudan University
    Fudan University)

  • Wei Sun

    (Fudan University Shanghai Cancer Center
    Fudan University)

  • Kangjie Shen

    (Fudan University
    Fudan University)

  • Jingqin Zhong

    (Fudan University Shanghai Cancer Center
    Fudan University)

  • Wanlin Liu

    (Fudan University Shanghai Cancer Center
    Fudan University)

  • Zixu Gao

    (Fudan University
    Fudan University)

  • Yu Xu

    (Fudan University Shanghai Cancer Center
    Fudan University)

  • Lu Wang

    (Fudan University
    Fudan University)

  • Tu Hu

    (Fudan University Shanghai Cancer Center
    Fudan University)

  • Ming Ren

    (Fudan University
    Fudan University)

  • Yinlam Li

    (Fudan University
    Fudan University)

  • Yu Zhu

    (Fudan University
    Fudan University)

  • Shaoluan Zheng

    (Fudan University)

  • Ming Zhu

    (Fudan University
    Fudan University)

  • Rongkui Luo

    (Fudan University)

  • Yanwen Yang

    (Fudan University
    Fudan University)

  • Yingyong Hou

    (Fudan University)

  • Fazhi Qi

    (Fudan University
    Fudan University)

  • Yuhong Zhou

    (Fudan University)

  • Yong Chen

    (Fudan University Shanghai Cancer Center
    Fudan University)

  • Jianying Gu

    (Fudan University
    Fudan University
    Fudan University)

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.

Suggested Citation

  • Chuanyuan Wei & Wei Sun & Kangjie Shen & Jingqin Zhong & Wanlin Liu & Zixu Gao & Yu Xu & Lu Wang & Tu Hu & Ming Ren & Yinlam Li & Yu Zhu & Shaoluan Zheng & Ming Zhu & Rongkui Luo & Yanwen Yang & Yingy, 2023. "Delineating the early dissemination mechanisms of acral melanoma by integrating single-cell and spatial transcriptomic analyses," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43980-y
    DOI: 10.1038/s41467-023-43980-y
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