ArticleCancer cell international2021
Deregulation of angiopoietin-like 4 slows ovarian cancer progression through vascular endothelial growth factor receptor 2 phosphorylation.
Article in Cancer cell international, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Emerging roles of angiopoietin‑like 4 in human tumors (Review).International journal of oncology · 2025Review
- ANGPTL4 regulates ovarian cancer progression by activating the ERK1/2 pathway.Cancer cell international · 2024Article
- ANGPTL4 accelerates ovarian serous cystadenocarcinoma carcinogenesis and angiogenesis in the tumor microenvironment by activating the JAK2/STAT3 pathway and interacting with ESM1.Journal of translational medicine · 2024Article
- High-fat diet and obesity are associated with differential angiogenic gene expression in epithelial ovarian cancer.Gynecologic oncology · 2023Article
- Unrestricted Ketogenic Diet Feeding Enhances Epithelial Ovarian Cancer Growth In Vivo.Nutrients · 2023Article
- An integrated bioinformatic analysis of bulk and single-cell sequencing clarifies immune microenvironment and metabolic profiles of lung adenocarcinoma to predict immunotherapy efficacy.Frontiers in cell and developmental biology · 2023Article
- ANGPTL4 functions as an oncogene through regulation of the ETV5/CDH5/AKT/MMP9 axis to promote angiogenesis in ovarian cancer.Journal of ovarian research · 2022Article
- Cytokines: Can Cancer Get the Message?Cancers · 2022Review
- TAZ Regulates the Cisplatin Resistance of Epithelial Ovarian Cancer Cells via the ANGPTL4/SOX2 Axis.Analytical cellular pathology (Amsterdam) · 2022Article
- Silencing of Angiopoietin-Like Protein 4 (Angptl4) Decreases Inflammation, Extracellular Matrix Degradation, and Apoptosis in Osteoarthritis via the Sirtuin 1/NF-Oxidative medicine and cellular longevity · 2022Article
- Identification and validation of a novel glycolysis-related gene signature for predicting the prognosis in ovarian cancer.Cancer cell international · 2021Article
- Identification of Hypoxia Signature to Assess the Tumor Immune Microenvironment and Predict Prognosis in Patients with Ovarian Cancer.International journal of endocrinology · 2021Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAs a tissue-specific proangiogenic or antiangiogenic agent, angiopoietin-like 4 (ANGPTL4) has recently gained attention in many diseases, such as metabolic syndrome, cardiovascular disease and cancer. However, the roles of ANGPTL4 in angiogenesis and tumor growth in epithelial ovarian cancer, the most lethal gynecologic malignancy, remain unclear.
objectiveTo identify a novel mechanism of ANGPTL4 inhibition in epithelial ovarian cancer.
methodsWestern blot, quantitative reverse transcription PCR, and immunofluorescence analyses were applied to evaluate ANGPTL4 expression in ovarian cancer cell lines. Cell proliferation, migration, and invasion were investigated through 5-ethynyl-2'-deoxyuridine (EdU) incorporation, CCK-8 and Transwell assays. The expression of epithelial-mesenchymal transition (EMT)-related proteins in ovarian cancer cells and tumor-bearing mice was evaluated. CD31 staining was used to identify tumor angiogenesis. Immunoprecipitation was performed to examine the regulatory relationship between ANGPTL4 and the vascular endothelial growth factor receptor 2 (VEGFR2)/vascular endothelial (VE)-cadherin/Src complex. VEGFR2 phosphorylation at Y949 and VE-cadherin expression were assessed by western blotting. Inactivation of VEGFR2 Y949 phosphorylation was achieved in a MISIIR-TAg VEGFR2
resultsHere, we demonstrated that ANGPTL4 was overexpressed in A2780 and CAOV3 ovarian cancer cells. In vitro assays indicated that inhibition of ANGPTL4 by lentiviral small interfering RNA does not alter ovarian cancer cell proliferation, migration, invasion, and EMT, while ANGPTL4 silencing exhibited significant inhibitory effects on tumor angiogenesis, growth, and metastasis in vivo. Immunoprecipitation analysis showed that suppression of ANGPTL4 was accompanied by dissociation of the VEGFR2/VE-cadherin/Src complex and phosphorylation of VEGFR2 Y949 in A2780 and CAOV3 ovarian tumors. Inactivation of VEGFR2 Y949 phosphorylation in MISIIR-TAg VEGFR2
conclusionsOverall, our results indicate that ANGPLT4 silencing delays tumor progression in specific types of ovarian cancer and may be a potential target for individualized treatment of ovarian cancer.
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