Metadherin enhances vulnerability of cancer cells to ferroptosis.

ABSTRACT: Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death driven by lipid hydroperoxides within biological membranes. Although therapy-resistant mesenchymal-high cancers are particularly vulnerable to ferroptosis inducers, especially phospholipid glutathione peroxidase 4 (GPx4) inhibitors, the underlying mechanism is yet to be deciphered. As such, the full application of GPx4 inhibitors in cancer therapy remains challenging. Here we demonstrate that metadherin (MTDH) confers a therapy-resistant mesenchymal-high cell state and enhanced sensitivity to inducers of ferroptosis. Mechanistically, MTDH inhibited GPx4, as well as the solute carrier family 3 member 2 (SLC3A2, a system X_c^- heterodimerization partner), at both the messenger RNA and protein lev

SUBMITTER: Bi J 

PROVIDER: S-EPMC6746770 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature