ArticleJournal of experimental & clinical cancer research : CR2019
Angiotensin II promotes ovarian cancer spheroid formation and metastasis by upregulation of lipid desaturation and suppression of endoplasmic reticulum stress.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 2 of them syntheses that pooled it.
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Who cites it
48 citing papers in PubMed, 2 syntheses or guidelines pooled it, 68 citations in OpenAlex.
- The interaction between endoplasmic reticulum stress and ferroptosis in ovarian diseases.Journal of ovarian research · 2026Pooled it
- The role of lipid metabolic reprogramming in tumor microenvironment.Theranostics · 2023Pooled it
- The Bidirectional Role of Cellular Senescence in the Treatment of Ovarian Cancer.Biomedicines · 2026Review
- Based on artificial intelligence-assisted generation and in-depth in-silico evaluation of potential inhibitors targeting Stearoyl-CoA desaturase 1 (SCD-1).Scientific reports · 2026Article
- Exploratory Analysis of Plasma Angiotensin-Converting Enzyme 2 and Angiotensin Peptides as Candidate Discriminatory Signals in Breast Cancer: A Pilot Case-Control Study.Biomedicines · 2026Article
- Review
- Impact of Antihypertensive Treatment on Outcomes of Adjuvant Bevacizumab for Ovarian Cancer (IATRO), Results from a Nationwide Emulated Clinical Trial.Clinical pharmacology and therapeutics · 2026Article
- Candesartan cilexetil as a repurposed therapeutic candidate for nasopharyngeal carcinoma: Integrated in vitro and in silico analyses.EXCLI journal · 2026Article
- Post-translational modifications in anaplastic thyroid carcinoma: biological mechanisms and therapeutic potential.Cancer cell international · 2025Review
- Age-related and postmenopausal breast cancer progression and treatment management: The significance of pro-inflammatory cytokines and CXC chemokines.Genes & diseases · 2025Review
- The Renin-Angiotensin-Aldosterone System (RAAS): Beyond Cardiovascular Regulation.Veterinary sciences · 2025Review
- AGTR1 potentiates the chemotherapeutic efficacy of cisplatin in esophageal carcinoma through elevation of intracellular CaInternational journal of oncology · 2025Article
- Beyond tumor‑associated macrophages involved in spheroid formation and dissemination: Novel insights for ovarian cancer therapy (Review).International journal of oncology · 2024Review
- Effects of super-enhancers in cancer metastasis: mechanisms and therapeutic targets.Molecular cancer · 2024Review
- Advances in regulation and function of stearoyl-CoA desaturase 1 in cancer, from bench to bed.Science China. Life sciences · 2023Review
- The renin-angiotensin-aldosterone system (RAAS) signaling pathways and cancer: foes versus allies.Cancer cell international · 2023Review
- Targeting endoplasmic reticulum stress signaling in ovarian cancer therapy.Cancer biology & medicine · 2023Review
- Lymphatic vasculature in ovarian cancer.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- BZW2 Inhibition Reduces Colorectal Cancer Growth and Metastasis.Molecular cancer research : MCR · 2023Article
- Antiproliferative and apoptotic effects of telmisartan in human glioma cells.Cancer cell international · 2023Article
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundAngiotensin II (ANGII) and its receptor (AGTR1) have been proposed as significant contributors to metastasis in multiple cancers. Further, high AGTR1 levels are associated with poor epithelial ovarian cancer (EOC) outcomes. However, the mechanistic basis for these effects is unknown. Recent studies have suggested that ovarian cancer metastasis is highly dependent on the formation of multicellular spheroids (MCS). To understand the associations between the ANGII/AGTR1 pathway and cancer outcomes, we evaluated the effects of ANGII on MCS formation by ovarian cancer cells and used a proteomic approach to analyze the mechanistic basis.
methodsWe used the data from the GENT database and immunohistochemistry staining to assess the AGTR1 expression in epithelial ovarian cancer (EOC) patients and to assess its role in cancer progression. Colony formation assay, 3D culture assay, and transwell assays were used to analyze the effect of ANGII on the MCS formation and cell migration. The signaling pathways of AGTR1 and transactivation of epidermal growth factor receptor (EGFR) transactivation were investigated by the western blotting analysis. Xenograft models were used to determine the role of AGTR1 in ovarian cancer metastasis. ANGII release from ovarian cancer cells and ANGII levels in the EOC ascites fluid were measured by immunoassay. A shotgun proteomic approach was used to explore the detail molecular mechanism. Modulation of lipid desaturation and endoplasmic reticulum stress were verified by the in vitro and in vivo functional assays.
resultsAGTR1 expression was negatively correlated with EOC prognosis. AGTR1activation significantly enhanced the MCS formation and cell migration. ANGII triggered both of the classical AGTR1 pathway and the EGFR transactivation. ANGII administration increased peritoneal metastasis. In addition, ovarian cancer cells secreted ANGII and enhanced cancer metastasis in a positive feedback manner. Based on the proteomic data, lipid desaturation was activated by induction of stearoyl-CoA desaturase-1 (SCD1), which suggests that inhibition of SCD1 may significantly reduce MCS formation by increasing endoplasmic reticulum stress.
conclusionsANGII promotes MCS formation and peritoneal metastasis of EOC cells. AGTR1 activation increases the lipid desaturation via SCD1 upregulation, which ultimately reduces endoplasmic reticulum stress in MCS. This mechanism explained the association between high levels of AGTR1 and poor clinical outcomes in EOC patients.
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