Disruption of NF-κB-Mediated Copper Homeostasis Sensitizes Breast Cancer to Cuproptosis.

ABSTRACT: Copper plays a key role in inflammation and recent tumorigenesis. However, copper homeostasis and its role in cuproplasia and cuproptosis for cancer intervention remain incompletely explored. Here, it is unveiled that copper enhances the NF-κB pathway by directly binding to transforming growth factor β-activated kinase 1 (TAK1), thereby promoting TRAF2 interaction with and mediation of TAK1 ubiquitination and activation, leading to IκB kinase β (IKKβ) activation and mediating copper's inflammatory and oncogenic functions. Notably, copper is indispensable for TNFα/LPS-induced NF-κB activation and subsequent PD-L1 promotion. Thus, copper chelators offer protection against acute infection in murine models. Meanwhile, NF-κB represses copper uptake by negatively controlling the expression of co

SUBMITTER: Zhang X 

PROVIDER: S-EPMC12713080 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature