312-Hypoxia Shifts Melanoma Ferroptosis Reliance to FSP1

Paper Talk · Dec 12, 2025 · 13m

The research examines the adaptations utilized by metastatic melanoma cells in the specialized lymph node microenvironment, revealing a vulnerability in their ferroptosis defense system. The hypoxic conditions found in the LNs trigger the breakdown of the primary anti-ferroptosis enzyme, glutathione peroxidase 4 (GPX4), via ubiquitin-proteasome degradation. This loss of GPX4 dependence forces the melanoma cells to switch reliance to an alternative protective protein, the ferroptosis suppressor protein 1 (FSP1), which is found accumulating at perinuclear lysosomes. Functionally, this shift…