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Cell Stem Cell. 2017 Mar 2;20(3):303-314.e5. doi: 10.1016/j.stem.2016.11.004. Epub 2016 Dec 29.

Lipid Desaturation Is a Metabolic Marker and Therapeutic Target of Ovarian Cancer Stem Cells.

Author information

1
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
2
Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
3
Department of Obstetrics and Gynecology, Indiana University, Indianapolis, IN 46202, USA.
4
Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
5
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.
6
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.
7
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.

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.

KEYWORDS:

NF-κB; Raman spectroscopic imaging; SCD1; cancer stem cells; lipid desaturation; ovarian cancer

PMID:
28041894
PMCID:
PMC5337165
DOI:
10.1016/j.stem.2016.11.004
[Indexed for MEDLINE]
Free PMC Article

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