Journal
CANCER BIOLOGY & THERAPY
Volume 22, Issue 2, Pages 164-174Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15384047.2021.1883414
Keywords
NF-κ B; stearoyl-CoA-desaturase 1; ceramide; serine palmitoyl-transferase 1; ceramide synthase 6; monounsaturated fatty acids
Categories
Funding
- National Natural Science Foundation of China [81603145]
- XMU Training Program of Innovation and Enterpreneurship for Undergraduates [2019Y1223]
- Fundamental Research Funds for the Central Universities [20720200015]
- Fujian Provincial Natural Science Foundation [2017J01146]
- Fujian Health-Education Research Grant [WKJ2016-2-03]
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SCD1 deficiency induces apoptosis in colorectal cancer cells by promoting ceramide de novo synthesis, with NF-kappa B pathway playing a crucial role in this process. Reduced levels of MUFAs contribute to the effects of SCD1 inhibition on cancer cell growth and gene expression.
Stearoyl-CoA-desaturase 1 (SCD1) deficiency mediates apoptosis in colorectal cancer cells by promoting ceramide de novo synthesis. The mechanisms underlying the cross-talk between SCD1 and ceramide synthesis have not been explored. We treated colorectal cancer cells with an SCD1 inhibitor and examined the effects on gene expression, cell growth, and cellular lipid contents. The main effect of SCD1 inhibition on the fatty acid contents of colorectal cancer cells was a decrease in monounsaturated fatty acids (MUFAs). RNA sequencing (RNA-seq) showed that the most intense alteration of gene expression after SCD1 inhibition occurred in the NF-kappa B signaling pathway. Further experiments revealed that SCD1 inhibition resulted in increased levels of phosphorylated NF-kappa B p65 and increased nuclear translocation of NF-kappa B p65. Treatment with an NF-kappa B inhibitor eliminated several effects of SCD1 inhibition, mainly including overexpression of serine palmitoyltransferase1 (SPT1), elevation of dihydroceramide contents, and suppression of cell growth. Furthermore, treatment with supplemental oleate counteracted the SCD1-induced NF-kappa B activation and downstream effects. In summary, our data demonstrate that the NF-kappa B pathway plays a role in SCD1 deficiency-induced ceramide de novo synthesis in colorectal cancer cells, and that reduced MUFA levels contribute to the course.
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