ArticleCell communication and signaling : CCS2025
Upregulated FSP1 by GPD1/1L mediated lipid droplet accumulation enhances ferroptosis resistance and peritoneal metastasis in gastric cancer.
Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Article
- New Functions of Mitochondrial Dysfunction in Gastric Cancer: From Molecular Processes to Potential Treatments.International journal of molecular sciences · 2026Review
- Androgen Receptor-Induced Lactoferrin Accelerates Prostate Tumorigenesis Through Modulating Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Intracellular lipid droplets positively regulate the dormancy of colorectal cancer cells depending on ELF1-ACSL5 signaling.Journal of experimental & clinical cancer research : CR · 2026Article
- Ferroptosis: The dawn of reversing drug resistance in digestive cancers.Genes & diseases · 2026Review
- OSBPL2-mediated lipid metabolism alteration governs lung cancer stem cells properties.Stem cell research & therapy · 2026Article
- Ferroptosis and metastasis: molecular checkpoints, microenvironmental dynamics, and therapeutic opportunities.Molecular cancer · 2026Review
- Effects of aging and anti-aging dietary restriction on regulators of the [NADPH]/[NADPFree radical biology & medicine · 2025Review
- Proteomic analysis of Burkitt lymphoma tissues: insights into the impact of age and EBV infection on protein expression and molecular characteristics.Discover oncology · 2025Article
- TIGD6 in gastric cancer: exploring its prognostic value and therapeutic potential through molecular and clinical investigations.European journal of medical research · 2025Article
- Roles and Prospective Applications of Ferroptosis Suppressor Protein 1 (FSP1) in Malignant Tumor Treatment.Current oncology (Toronto, Ont.) · 2025Review
- Mitochondrial metabolism and cancer therapeutic innovation.Signal transduction and targeted therapy · 2025Review
- Ferroptosis in Hypertriglyceridemic Acute Pancreatitis: Mechanisms and Therapeutic Implications.Journal of inflammation research · 2025Review
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Authors and funding
13 authors.
Funding
Abstract
To successfully metastasize, cancer cells must evade detachment induced cell death, known as anoikis. Unraveling the mechanisms that gastric cancer (GC) circumvent anoikis and achieve peritoneal metastasis especially during unanchored growth, could significantly improve patient outcomes. Our study reveals that GC cells exhibit increased lipid peroxidation, MDA production, and cell death during suspension culture, which can be mitigated by the intervention with liproxstatin-1 and ferrostatin-1. We discovered that oleic acid (OA) or adipocytes stimulate lipid accumulation in GC cells, thereby inhibiting lipid peroxidation and cell death. Lipid mass spectrometry confirmed an upregulation of triglyceride synthesis, indicating that the accumulation of lipid droplet may confer resistance to ferroptosis during suspension growth. In vitro assays demonstrated that OA not only induces lipid droplet accumulation but also upregulates the expression of ferroptosis suppressor protein 1 (FSP1), a process that can be abrogated by the double knockout of GPD1/1L genes. Additionally, we have demonstrated that a decrease in the ubiquitination of FSP1 in GC cells upon lipid droplet accumulation, as well as silencing or pharmacological targeting FSP1, promotes ferroptosis and disrupts the peritoneal metastatic potential of GC cells. Collectively, our findings highlight the potential of FSP1 as a promising therapeutic target for metastatic gastric cancer.
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