Significance

Unsaturated fatty acids are critical for maintaining membrane fluidity, cellular signaling, and lipid storage. Stearoyl-CoA desaturase (SCD) regulates the dynamics between saturated and unsaturated fatty acids. How SCD is involved in cancer cell fate decisions remains incompletely understood. Here, we leveraged transcriptomics, lipidomics, and single-cell stimulated Raman scattering microscopy to show that increased levels of lipid unsaturation promoted by SCD protected cancer cells against endoplasmic reticulum stress-induced apoptosis. Reduced levels of unsaturated fat caused either by SCD depletion or by SCD inhibition coupled with a diet rich in saturated fat blocked cancer cell growth in vitro and tumor progression in vivo. These findings support the concept of targeting the lipid balance as a cancer target

https://www.pnas.org/doi/abs/10.1073/pnas.2203480119