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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 303-314.e5 |
| Journal | Cell stem cell |
| Volume | 20 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2 2017 |
Funding
The authors thank Leelyn Chong and Drs. Bin Liu, Chi Zhang, and Bakhtiyor Yakubov for technical support. The authors acknowledge the use of the metabolite profiling facility of the Bindley Bioscience Center at Purdue University. This work was supported by a VA Merit Award (BX000792-05A1), the NCI (CA198409 to D.M. and CA182608 to J.-X.C.), the Walther Cancer Foundation (to J.-X.C.), and the NIH (P30CA023168). J.L. and J.-X.C. are co-founders of Resarci Therapeutics LLC.
Keywords
- NF-κB
- Raman spectroscopic imaging
- SCD1
- cancer stem cells
- lipid desaturation
- ovarian cancer
ASJC Scopus subject areas
- Molecular Medicine
- Genetics
- Cell Biology
