Role of lipids in melanoma metastasis
Tumor microenvironment (TME) impacts cancer cells by sending out signals, but the TME cues that impact metastasis and tropism are still incompletely understood.
The researchers show that young subcutaneous adipocytes provide lipids and phosphatidylcholine to melanoma cells, which activates PI3K-AKT, OXPHOS, and oxidative stress. High OXPHOS reduces metastatic burden and associates with lung tropism.
Conversely, aged subcutaneous adipocytes provide ceramides to melanoma cells, which activates S1P-STAT3-IL-6 signaling, increasing total metastatic burden and liver metastasis.
The authors show that inhibiting OXPHOS in the young TME or blocking the IL-6 receptor in the aged TME reduces the age-specific patterns of metastasis imposed by lipid availability.
https://www.cell.com/cancer-cell/fulltext/S1535-6108(25)00138-2
