ArticleNature cell biology2026
Peritumoural adipose tissue promotes ferroptosis resistance by 3-hydroxykynurenine-mediated suppression of ferritinophagy.
Article in Nature cell biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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Who cites it
5 citing papers in PubMed.
- Tryptophan metabolism in colorectal cancer: From mechanistic insights to novel therapeutic strategies.Clinical and translational medicine · 2026Review
- Multidrug resistance in cancer: current understandings and future perspective.Molecular biomedicine · 2026Review
- Targeting PCSK9 in Vascular Smooth Muscle Cells: An Effective Strategy to Suppress Ferroptosis and Attenuate Abdominal Aortic Aneurysm Progression.Cell proliferation · 2026Article
- Peritumoural adipose tissue promotes ferroptosis resistance by 3-hydroxykynurenine-mediated suppression of ferritinophagy.Nature cell biology · 2026Article
- Bidirectional regulation between ferroptosis and tumor-associated macrophages: mechanisms, strategies, and therapeutic perspectives.Frontiers in oncology · 2026Review
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
The peritumoural adipose tissue (PAT) is a key contributor to cancer therapy resistance, yet its role in regulating ferroptosis remains unclear. Here we demonstrate that PAT confers ferroptosis resistance to cancer cells by upregulating ferritin (FTH1/FTL) and sequestering intracellular iron. PAT-derived kynurenine (KYN) was identified as the principal mediator. KYN is taken up by cancer cells and metabolized to 3-hydroxykynurenine, which directly binds to nuclear receptor coactivator 4 (NCOA4). This interaction inhibits NCOA4-mediated ferritinophagy, preventing ferritin degradation and limiting the free iron pool required for ferroptosis. In murine models, pharmacological inhibition of the KYN pathway synergized with PD-1 blockade to overcome ferroptosis resistance and suppress tumour progression. These findings reveal a PAT-KYN-ferritinophagy axis that promotes ferroptosis resistance, highlighting the potential of targeting adipose-tumour cross-talk to enhance immunotherapy in PAT-associated tumours.
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Registered trials
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