Lymph node environment drives FSP1 targetability in metastasizing melanoma.

ABSTRACT: Ferroptosis has emerged as an actionable target to eliminate therapy-resistant and metastatic cancers¹. However, which ferroptosis surveillance systems may offer a therapeutic window to leverage redox maladaptation in cancer remains unclear. In melanoma, glutathione peroxidase 4 (GPX4) impedes ferroptosis during haematogenous metastasis, but is dispensable during lymphatic metastasis². Here, using a metastatic mouse melanoma model selected for lymph node metastasis, we show that lymph-node-derived metastatic cells exhibit markedly diminished expression of glutamate-cysteine ligase (GCLC) and reduced glutathione (GSH) levels relative to their parental counterparts. This metabolic shift occurs within the hypoxic lymphatic niche. Under comparable low-oxygen conditions, G

SUBMITTER: Palma M 

PROVIDER: S-EPMC12779575 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature