Whitney S Henry, Sebastian Müller, Jia-Shu Yang, Sarah Innes-Gold, Sunny Das, Ferenc Reinhardt, Kim Sigmund, Vaishnavi V Phadnis, Zhengpeng Wan, Elinor Eaton, Julio L Sampaio, George W Bell, Amartya Viravalli, Paula T Hammond, Roger D Kamm, Adam E Cohen, Natalie Boehnke, Victor W Hsu, Kandice R Levental, Raphaël Rodriguez, Robert A Weinberg
Cancer cell fate has been widely ascribed to mutational changes within protein-coding genes associated with tumor suppressors and oncogenes. In contrast, the mechanisms through which the biophysical properties of membrane lipids influence cancer cell survival, dedifferentiation and metastasis have received little scrutiny. Here, we report that cancer cells endowed with a high metastatic ability and cancer stem cell-like traits employ ether lipids to maintain low membrane tension and high membrane fluidity. Using genetic approaches and lipid reconstitution assays, we show that these ether lipid-regulated biophysical properties permit non-clathrin-mediated iron endocytosis via CD44, leading directly to significant increases in intracellular redox-active iron and enhanced ferroptosis susceptibility...
March 21, 2024: bioRxiv