Delineating the early dissemination mechanisms of acral melanoma by integrating single-cell and spatial transcriptomic analyses
Open accessAbstract
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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Endothelial Pim3 kinase protects the vascular barrier during lung metastasis
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- Authors
- Wei, C., Sun, W., Shen, K., Zhong, J., Liu, W., Gao, Z., Xu, Y., Wang, L., Hu, T., Ren, M., Li, Y., Zhu, Y., Zheng, S., Zhu, M., Luo, R., Yang, Y., Hou, Y., Qi, F., Zhou, Y., Chen, Y., & Gu, J.
- Affiliations
- Fudan University (CN)
- Shanghai Medical College of Fudan University (CN)
- Corresponding author
- Zhou, Yuhong
- Chen, Yong
- Gu, Jianying
- ORCID
- Venue
- Nature Communications
- Published
- 2023-12-08
- Volume
- 14
- Issue
- 1
- Pages
- 8119-8119
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC10709603
- OpenAlex
- W4389481108
- Cited by
- 49
- References
- 66
- Citations by year
- 2026: 20 · 2025: 19 · 2024: 10
- FWCI
- 5.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (82272891, 81972559, 82203528)
- Shanghai Shenkang Hospital Development Centre Project
- China Postdoctoral Science Foundation (2022M710769, 2022TQ0072)
- Shanghai Sailing Program
- Topics
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- acral melanoma, lymph node metastasis, metastasis, tumor heterogeneity, immunosuppressive tumor microenvironment, intercellular communication, fatty acid oxidation, MITF, etomoxir, metabolic reprogramming
- MeSH terms
- Humans, Lymphatic Metastasis, Melanoma, Skin Neoplasms, Gene Expression Profiling, Tumor Microenvironment, Transcriptome
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