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DMT1 Inhibitors Kill Cancer Stem Cells by Blocking Lysosomal Iron Translocation

10 Jun 2020Chemistry – A European Journal

DOI : 10.1002/chem.202000159

Authors

Andreea L. Turcu, Antoine Versini, Nadjib Khene, Christine Gaillet, Tatiana Cañeque, Sebastian Müller, Raphaël Rodriguez

Abstract

Abstract

Cancer stem cells (CSC) constitute a cell subpopulation in solid tumors that is responsible for resistance to conventional chemotherapy, metastasis and cancer relapse. The natural product Salinomycin can selectively target this cell niche by directly interacting with lysosomal iron, taking advantage of upregulated iron homeostasis in CSC. Here, inhibitors of the divalent metal transporter 1 (DMT1) have been identified that selectively target CSC by blocking lysosomal iron translocation. This leads to lysosomal iron accumulation, production of reactive oxygen species and cell death with features of ferroptosis. DMT1 inhibitors selectively target CSC in primary cancer cells and circulating tumor cells, demonstrating the physiological relevance of this strategy. Taken together, this opens up opportunities to tackle unmet needs in anti‐cancer therapy.

Members

RAPHAEL RODRIGUEZ

Directeur de recherche CNRS

TATIANA CANEQUE COBO

Ingénieur de recherche CNRS

CHRISTINE GAILLET

Ingénieur d'études CNRS

SEBASTIAN MULLER

Chargé de recherche Inserm