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

Junjie Li, Salvatore Condello, Jessica Thomes-Pepin, Xiaoxiao Ma, Yu Xia, Thomas Hurley, Daniela Matei, Ji Xin Cheng

Research output: Contribution to journalArticle

107 Citations (Scopus)

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. Cheng and colleagues using Raman spectroscopic imaging find that ovarian cancer stem cells contain unusually high levels of unsaturated lipids and show evidence that this metabolic difference could be used as a marker for these cells and as a new target for CSC-specific therapy.

Original languageEnglish (US)
JournalCell Stem Cell
DOIs
StateAccepted/In press - Jan 4 2016

Fingerprint

Neoplastic Stem Cells
Ovarian Neoplasms
Lipids
Therapeutics
Cell- and Tissue-Based Therapy
Single-Cell Analysis
Raman Spectrum Analysis
Mass Spectrometry
Stem Cells
Cell Line

Keywords

  • Cancer stem cells
  • Lipid desaturation
  • NF-κB
  • Ovarian cancer
  • Raman spectroscopic imaging
  • SCD1

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

Cite this

Lipid Desaturation Is a Metabolic Marker and Therapeutic Target of Ovarian Cancer Stem Cells. / Li, Junjie; Condello, Salvatore; Thomes-Pepin, Jessica; Ma, Xiaoxiao; Xia, Yu; Hurley, Thomas; Matei, Daniela; Cheng, Ji Xin.

In: Cell Stem Cell, 04.01.2016.

Research output: Contribution to journalArticle

Li, Junjie ; Condello, Salvatore ; Thomes-Pepin, Jessica ; Ma, Xiaoxiao ; Xia, Yu ; Hurley, Thomas ; Matei, Daniela ; Cheng, Ji Xin. / Lipid Desaturation Is a Metabolic Marker and Therapeutic Target of Ovarian Cancer Stem Cells. In: Cell Stem Cell. 2016.
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