RETRACTED ARTICLE: Vasculogenic mimicry formation in EBV-associated epithelial malignancies
Open accessAbstract
Epstein-Barr virus (EBV)-associated epithelial cancers, including nasopharyngeal carcinoma (NPC) and approximately 10% of gastric cancers, termed EBVaGC, represent 80% of all EBV-related malignancies. However, the exact role of EBV in epithelial cancers remains elusive. Here, we report that EBV functions in vasculogenic mimicry (VM). Epithelial cancer cells infected with EBV develop tumor vascular networks that correlate with tumor growth, which is different from endothelial-derived angiogenic vessels and is VEGF-independent. Mechanistically, activation of the PI3K/AKT/mTOR/HIF-1α signaling cascade, which is partly mediated by LMP2A, is responsible for EBV-induced VM formation. Both xenografts and clinical samples of NPC and EBVaGC exhibit VM histologically, which are correlated with AKT and HIF-1α activation. Furthermore, although anti-VEGF monotherapy shows limited effects, potent synergistic antitumor activities are achieved by combination therapy with VEGF and HIF-1α-targeted agents. Our findings suggest that EBV creates plasticity in epithelial cells to express endothelial phenotype and provides a novel EBV-targeted antitumor strategy.
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mTOR activity promotes angiogenesis by regulating HIF-1α transcription and translation.
“mTOR activity promotes angiogenesis by regulating HIF‐1α transcription and translation.”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [183]
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- Authors
- Xiang, T., Lin, Y.-X., Ma, W., Zhang, H.-J., Chen, K.-M., He, G.-P., Zhang, X., Xu, M., Feng, Q.-S., Chen, M.-Y., Zeng, M.-S., Zeng, Y.-X., & Feng, L.
- Affiliations
- Sun Yat-sen University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Sun Yat-sen University Cancer Center (CN)
- Corresponding author
- Lin, Yu-Xin
- Zeng, Yi-Xin
- Feng, Lin
- Venue
- Nature Communications
- Published
- 2018-11-27
- Volume
- 9
- Issue
- 1
- Pages
- 5009-5009
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6258759
- OpenAlex
- W2901895772
- Cited by
- 172
- References
- 60
- Citations by year
- 2026: 4 · 2025: 22 · 2024: 25 · 2023: 33 · 2022: 27 · 2021: 31 · 2020: 19 · 2019: 11
- FWCI
- 5.72
- Type
- journal article
- Language
- en
- Status
- Retracted
- Update notices
- retraction (2025-10-27)
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Natural Science Foundation of China (81672980, 2016YFC0902000, 81430059, 81874130, 81874129)
- China Postdoctoral Science Foundation
- Topics
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- Epstein-Barr virus, vasculogenic mimicry, nasopharyngeal carcinoma, EBV-associated gastric cancer, LMP2A, PI3K/AKT/mTOR pathway, HIF-1α, endothelial phenotype, combination therapy, antitumor strategy
- MeSH terms
- Axitinib, Animals, Epithelial Cells, Herpesvirus 4, Human, Female, Mice, Inbred BALB C, Mice, Nude, Mustard Compounds, Nasopharyngeal Neoplasms, Neovascularization, Pathologic, Phenylpropionates, Viral Matrix Proteins, Signal Transduction, Genome, Viral, Phosphatidylinositol 3-Kinases, Gene Expression Profiling, Vascular Endothelial Growth Factor A, Cell Line, Tumor, Proto-Oncogene Proteins c-akt, Hypoxia-Inducible Factor 1, alpha Subunit, TOR Serine-Threonine Kinases
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