title: Lipid Desaturation Is a Metabolic Marker and Therapeutic Target of Ovarian Cancer Stem Cells.
abstract: Lack of sensitive single-cell analysis tools has limited the characterization of metabolic activity in cancer stem cells. By hyperspectral-stimulated Raman scattering imaging of single living cells and mass spectrometry analysis of extracted lipids, we report here significantly increased levels of unsaturated lipids in ovarian cancer stem cells (CSCs) as compared to non-CSCs. Higher lipid unsaturation levels were also detected in CSC-enriched spheroids compared to monolayer cultures of ovarian cancer cell lines or primary cells. Inhibition of lipid desaturases effectively eliminated CSCs, suppressed sphere formation in vitro, and blocked tumor initiation capacity in vivo. Mechanistically, we demonstrate that nuclear factor κB (NF-κB) directly regulates the expression levels of lipid desaturases, and inhibition of desaturases blocks NF-κB signaling. Collectively, our findings reveal that increased lipid unsaturation is a metabolic marker for ovarian CSCs and a target for CSC-specific therapy.
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Junjie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Condello
authors.affiliation: Department of Obstetrics and Gynecology, Indiana University, Indianapolis, IN 46202, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Thomes-Pepin
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Hurley
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Jesse Brown VA Medical Center, Chicago, IL 60612, USA; Robert H. Lurie Comprehensive Cancer Center, Chicago, IL 60611, USA. Electronic address: daniela.matei@northwestern.edu.
authors.forename: Daniela
authors.initials: D
authors.lastname: Matei
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA; Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA; Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA. Electronic address: jcheng@purdue.edu.
authors.forename: Ji-Xin
authors.initials: JX
authors.lastname: Cheng
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D015536:Down-Regulation / Q000235:genetics; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D016328:NF-kappa B / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D008055:Lipids; D016328:NF-kappa B; D044943:Fatty Acid Desaturases; D000444:Aldehyde Dehydrogenase
keywords: NF-κB; Raman spectroscopic imaging; SCD1; cancer stem cells; lipid desaturation; ovarian cancer