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Cancer cells with high metastatic capability and cancer stem cell-like traits use ether lipids to sustain low membrane tension and high membrane fluidity. Ether-lipid–controlled properties enable non-clathrin-mediated iron endocytosis via CD44, elevating redox-active intracellular iron and increasing ferroptosis susceptibility. Loss of ether lipids also reduces extravasation, metastatic burden, and cancer stemness in vitro and in vivo.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/ether-lipids-influence-cancer-cell-fate-abstract-and-keywords/433530/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/ether-lipids-influence-cancer-cell-fate-abstract-and-keywords/433530.png","ImageObject",300,407,{"name":92,"@type":93},"Jiven","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role do ether lipids play in cancer cell fate?","Question",{"text":112,"@type":113},"Ether lipids help cancer cells maintain low membrane tension and high membrane fluidity, supporting malignant progression and cancer stem cell-like traits.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do ether lipids affect iron uptake and ferroptosis?",{"text":117,"@type":113},"Ether-lipid–regulated membrane properties permit non-clathrin-mediated iron endocytosis via CD44, increasing intracellular redox-active iron and enhancing ferroptosis susceptibility.",{"name":119,"@type":110,"acceptedAnswer":120},"What is the impact of losing ether lipids on metastasis-related behaviors?",{"text":121,"@type":113},"Loss of ether lipids attenuates extravasation, reduces metastatic burden, and diminishes cancer stemness in experimental in vitro and in vivo models.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},433530,1790883406,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},1099513958607,"https://ap-avatar.wpscdn.com/avatar/100002390cf8733938c?x-image-process=image/resize,m_fixed,w_180,h_180&k=1778829742770036399","bioRxiv preprint doi: [https://doi.org/10.1101/2024.03.20.585922](https://doi.org/10.1101/2024.03.20.585922); this version posted March 21, 2024. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY-NC-ND 4.0 International license.  \n1 Ether lipids influence cancer cell fate by modulating iron uptake 2  \n3 Whitney S. Henry 1 , Sebastian Müller2 , Jia-Shu Yang3 , Sarah Innes-Gold4 , Sunny Das 1 , 4 Ferenc Reinhardt 1 , Kim Sigmund 1 , Vaishnavi V. Phadnis 1,5 , Zhengpeng Wan6 , Elinor  \n5 Eaton 1 , Julio L. Sampaio7 , George W. Bell 1 , Amartya Viravalli8 , Paula T. Hammond9,10,15 , 6 Roger D. Kamm6,12,15 , Adam E. Cohen4,12,15 , Natalie Boehnke8 ,9,15 , Victor W. Hsu3,15 , 7 Kandice R. Levental 13,15 , Raphaël Rodriguez2,15,* and Robert A. Weinberg 1,5,14,15,*,\\#  \n8  \n9 1. Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA  \n10 2. Institut Curie, CNRS, INSERM, PSL Research University, Equipe Labellisée  \n11 Ligue Contre le Cancer, Paris 75005, France  \n12 3. Division of Rheumatology, Inflammation and Immunity, Brigham and Women’s  \n13 Hospital, and Dept. of Medicine, Harvard Medical School, Boston, MA 02115,  \n14 USA  \n15 4. Dept. of Chemistry and Chemical Biology, Harvard University, Cambridge, MA  \n16 02138, USA  \n17 5. Dept. of Biology, MIT, Cambridge, MA 02139, USA  \n18 6. Dept. of Biological Engineering, MIT, Cambridge, MA 02139, USA  \n19 7. Institut Curie, INSERM, Mines ParisTech, Paris 75005, France  \n20 8. Dept. of Chemical Engineering and Materials Science, University of Minnesota  \n21 Minneapolis, MN 55455, USA  \n22 9. Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA  \n23 10. Dept. of Chemical Engineering, MIT, Cambridge, MA 02139, USA 24 11. Dept. of Mechanical Engineering, MIT, Cambridge, MA 02139, USA 25 12. Dept. of Physics, Harvard University, Cambridge, MA 02138, USA  \n26 13. Dept. of Molecular Physiology and Biological Physics, Center for Membrane and  \n27 Cell Physiology, University of Virginia, Charlottesville, VA 22903, USA 28 14. Ludwig Center for Molecular Oncology, Cambridge, MA 02139, USA 29 15. Senior author  \n30 \\# Lead contact  \n31 *Correspondence: Raphaël Rodriguez, PhD ([raphael.rodriguez@curie.fr](raphael.rodriguez@curie.fr)) and Robert  \n32 A. Weinberg, PhD ([weinberg@wi.mit.edu](weinberg@wi.mit.edu)) 33  \n34  \n35  \n36  \n37  \n38  \n39  \n40  \n41  \n42  \n43  \n44  \n45  \nbioRxiv preprint doi: [https://doi.org/10.1101/2024.03.20.585922](https://doi.org/10.1101/2024.03.20.585922); this version posted March 21, 2024. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY-NC-ND 4.0 International license.  \n47 ABSTRACT  \n48 Cancer cell fate has been widely ascribed to mutational changes within protein-coding  \n49 genes associated with tumor suppressors and oncogenes. In contrast, the mechanisms  \n50 through which the biophysical properties of membrane lipids influence cancer cell  \n51 survival, dedifferentiation and metastasis have received little scrutiny. Here, we report  \n52 that cancer cells endowed with a high metastatic ability and cancer stem cell-like traits  \n53 employ ether lipids to maintain low membrane tension and high membrane fluidity.  \n54 Using genetic approaches and lipid reconstitution assays, we show that these ether  \n55 lipid-regulated biophysical properties permit non-clathrin-mediated iron endocytosis via  \n56 CD44, leading directly to significant increases in intracellular redox-active iron and  \n57 enhanced ferroptosis susceptibility. Using a combination of in vitro three-dimensional  \n58 microvascular network systems and in vivo animal models, we show that loss of ether  \n59 lipids also strongly attenuates extravasation, met","cbCaie6yzlsq9Ds9","https://ap.wps.com/l/cbCaie6yzlsq9Ds9","pdf",4946841,39,"English","# ABSTRACT\n# KEYWORDS\n# INTRODUCTION","[{\"question\":\"What role do ether lipids play in cancer cell fate?\",\"answer\":\"Ether lipids help cancer cells maintain low membrane tension and high membrane fluidity, supporting malignant progression and cancer stem cell-like traits.\"},{\"question\":\"How do ether lipids affect iron uptake and ferroptosis?\",\"answer\":\"Ether-lipid–regulated membrane properties permit non-clathrin-mediated iron endocytosis via CD44, increasing intracellular redox-active iron and enhancing ferroptosis susceptibility.\"},{\"question\":\"What is the impact of losing ether lipids on metastasis-related behaviors?\",\"answer\":\"Loss of ether lipids attenuates extravasation, reduces metastatic burden, and diminishes cancer stemness in experimental in vitro and in vivo models.\"}]","Ether lipids influence cancer cell fate - Abstract and keywords | PDF",1790664465,98]