ArticleProceedings of the National Academy of Sciences of the United States of America2022
Ovarian cancer cell fate regulation by the dynamics between saturated and unsaturated fatty acids.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 91 citations in OpenAlex.
- The Unsaturated/Saturated Fatty Acid Ratio: A Metabolic Hub and Therapeutic Vulnerability in Glioblastoma.Biomedicines · 2026Review
- The novel oleanolic acid derivative ZQL-4c modulates trastuzumab resistance in HER2+ breast cancer by inhibiting SCD-mediated lipid metabolism disorders.Cancer cell international · 2026Article
- Oleic acid fuels cisplatin-resistant ovarian cancer through FABP4-driven lipid uptake.Molecular metabolism · 2026Article
- Stearoyl-CoA Desaturase-1 Drives Tumor Growth by Interacting With Histone Deacetylase-2 and Deacetylating Nucleophosmin-1.MedComm · 2026Article
- Stiripentol induces ER stress and pyroptosis in pancreatic cancer cells under metabolic stress by dysregulating SFAs/UFAs homeostasis.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Natural Product Target Identification of Wheldone, a Fungal Metabolite, as a KIF11 Inhibitor in Ovarian Cancer Using the DiffPOP (Differential Protein Precipitation) Method.Molecular & cellular proteomics : MCP · 2026Article
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- High-Content SRS Imaging Unveils Altered Cholesterol Metabolism in Ovarian Cancers Under CAR-T Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Distinct metabolic profiles in lung adenocarcinomas presenting as solid or ground-glass opacities.NPJ precision oncology · 2026Article
- Nutritional modulation of metabolic signaling within the tumor microenvironment for cancer therapy.Molecular and cellular biochemistry · 2026Review
- Metabolic Dependency on De Novo Pyrimidine Synthesis Is a Targetable Vulnerability in Platinum-Resistant Ovarian Cancer.Cancer research · 2026Article
- Alterations in lipid metabolism and blood profile in gynecological cancers - potential strategies in diagnosis and treatment.Frontiers in physiology · 2026Review
- Stimulated Raman Scattering Imaging Enabled Biomarker Discovery for Precision Medicine.Chemical & biomedical imaging · 2025Review
- Metabolic syndrome promotes endometrial cancer by Oleic acid-mediated polyamine accumulation.Nature communications · 2025Article
- Photodynamic therapy simultaneously induces ferroptosis- and apoptosis-like lipid signatures in ovarian cancer cells.Cell death & disease · 2025Article
- Advances in ovarian cancer: biological insights, therapeutic innovations, and future perspectives.Journal of ovarian research · 2025Review
- Beyond light scattering: the effects of intralipid on benzoporphyrin derivative-sensitized photodynamic treatment in ovarian cancer cells.Journal of biomedical optics · 2025Article
- Exploring the significance of fatty acid metabolism reprogramming in the pathogenesis of cancer and anticancer therapy.Annals of medicine · 2025Review
- Nutrition-Based Paternal Influence on Gynecological Diseases in Female Offspring via Epigenetic Mechanisms.Nutrients · 2025Review
- Advanced vibrational microscopes for life science.Nature methods · 2025Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Fatty acids are an important source of energy and a key component of phospholipids in membranes and organelles. Saturated fatty acids (SFAs) are converted into unsaturated fatty acids (UFAs) by stearoyl Co-A desaturase (SCD), an enzyme active in cancer. Here, we studied how the dynamics between SFAs and UFAs regulated by SCD impacts ovarian cancer cell survival and tumor progression. SCD depletion or inhibition caused lower levels of UFAs vs. SFAs and altered fatty acyl chain plasticity, as demonstrated by lipidomics and stimulated Raman scattering (SRS) microscopy. Further, increased levels of SFAs resulting from SCD knockdown triggered endoplasmic reticulum (ER) stress response with brisk activation of IRE1α/XBP1 and PERK/eIF2α/ATF4 axes. Disorganized ER membrane was visualized by electron microscopy and SRS imaging in ovarian cancer cells in which SCD was knocked down. The induction of long-term mild ER stress or short-time severe ER stress by the increased levels of SFAs and loss of UFAs led to cell death. However, ER stress and apoptosis could be readily rescued by supplementation with UFAs and reequilibration of SFA/UFA levels. The effects of SCD knockdown or inhibition observed in vitro translated into suppression of intraperitoneal tumor growth in ovarian cancer xenograft models. Furthermore, a combined intervention using an SCD inhibitor and an SFA-enriched diet initiated ER stress in tumors growing in vivo and potently blocked their dissemination. In all, our data support SCD as a key regulator of the cancer cell fate under metabolic stress and point to treatment strategies targeting the lipid balance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.