C1/C2/C4 cells simultaneously exhibited stronger invasiveness and high expression of the tumor metastasis marker gene MITF, while for C3, similar to reported immunomodulatory clusters upregulated S100A1, S100B, this cell cluster promote AM metastasis by shaping a “cold” TME through microenvironmental conditioning rather than serving as metastatic diver cell clusters, highlighting the multifaceted roles of melanoma cells in AM ecosystems [5]. Here, S100A1 is linked to melanoma.