ArticleScientific reports2024
FADS2 confers SCD1 inhibition resistance to cancer cells by modulating the ER stress response.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- The pivotal role of SCD1 in digestive cancers: Bridging lipid metabolic reprogramming and programmed cell death (Review).International journal of oncology · 2026Review
- Subtype-specific mechanisms of lipid metabolism in gynecological malignancies and novel targeted intervention strategies (Review).Oncology letters · 2026Review
- Metabolic Reprogramming of Cancer Stem Cells: Targeting Lipid Flux and Mitochondrial Plasticity to Overcome Therapeutic Resistance.Cancer medicine · 2026Review
- The Latest Therapeutic Targets and New Drug Research of Metabolic Dysfunction-Associated Steatotic Liver Disease.Clinical pharmacology and therapeutics · 2026Review
- LMAN2 promotes breast cancer progression and deduces cell sensitivity to doxorubicin through stearoyl-CoA desaturase.Breast cancer research : BCR · 2026Article
- TOMM40/FADS2 Expression Ratio Predicts the Sensitivity to mTOR Inhibitors in Triple-Negative Breast Cancer.Cancer medicine · 2026Article
- Serum Palmitoleic Acid and Arachidonic Acid as a Noninvasive Screening Tool for Endometrial Cancer.Cancers · 2026Article
- METTL3- and IGF2BP1-associated m6A regulation of FADS2 contributes to lipid droplet accumulation and malignant progression in non-small cell lung cancer.Translational cancer research · 2026Article
- Targeting the lipid desaturation network in cancer: from metabolic plasticity to precision therapeutics.Journal of experimental & clinical cancer research : CR · 2026Review
- Mechanisms of fatty acid metabolism in tumor metastasis and targeted therapeutic strategies.Discover oncology · 2026Review
- Lipid Metabolic Reprogramming in Breast Cancer: Mechanisms and Emerging Therapeutic Strategies.Breast cancer (Dove Medical Press) · 2026Review
- Lipid metabolic reprogramming in colorectal cancer: Insights to mechanisms and therapeutics.World journal of gastrointestinal oncology · 2025Review
- Fatty Acid Desaturase: The Yin or Yang of Disease Pathology.Molecular diagnosis & therapy · 2025Review
- Fatty acid desaturases link cell metabolism pathways to promote proliferation of Epstein-Barr virus-infected B cells.PLoS pathogens · 2025Article
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Authors and funding
9 authors.
Funding
Abstract
Stearoyl-CoA desaturase 1 (SCD1) is an attractive target for cancer therapy. However, the clinical efficacy of SCD1 inhibitor monotherapy is limited. There is thus a need to elucidate the mechanisms of resistance to SCD1 inhibition and develop new therapeutic strategies for combination therapy. In this study, we investigated the molecular mechanisms by which cancer cells acquire resistance to endoplasmic reticulum (ER) stress-dependent cancer cell death induced by SCD1 inhibition. SCD1 inhibitor-sensitive and -resistant cancer cells were treated with SCD1 inhibitors in vitro, and SCD1 inhibitor-sensitive cancer cells accumulated palmitic acid and underwent ER stress response-induced cell death. Conversely, SCD1-resistant cancer cells did not undergo ER stress response-induced cell death because fatty acid desaturase 2 (FADS2) eliminated the accumulation of palmitic acid. Furthermore, genetic depletion using siRNA showed that FADS2 is a key determinant of sensitivity/resistance of cancer cells to SCD1 inhibitor. A549 cells, an SCD1 inhibitor-resistant cancer cell line, underwent ER stress-dependent cancer cell death upon dual inhibition of SCD1 and FADS2. Thus, combination therapy with SCD1 inhibition and FADS2 inhibition is potentially a new cancer therapeutic strategy targeting fatty acid metabolism.
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