Hypoxia induced epithelial-mesenchymal transition and vasculogenic mimicry formation by promoting Bcl-2/Twist1 cooperation
Abstract
Hypoxia plays a pivotal role in tumor progression. The functions of hypoxia and subsequent Bcl-2/Twist1 activation in epithelial-mesenchymal transition (EMT) and vasculogenic mimicry (VM) formation are currently unclear. This study aimed to investigate the role of Bcl-2/Twist1 cooperation in hypoxia-induced EMT and VM formation. In in vitro experiments, we found that hypoxia resulted in co-overexpression of Bcl-2 and Twist1, facilitated Twist1 nuclear translocation and promoted EMT and VM formation. Co-overexpression of Bcl-2 and Twist1 under normoxia could also induce EMT and promote VM formation. Furthermore, blocking Bcl-2 or Twist1 attenuated the effects of hypoxia on EMT progress and VM formation in hepatocellular carcinoma cells. In in vivo experiments, the mechanism by which hypoxia promoted Bcl-2 and Twist1 co-overexpression and induced EMT process and VM formation was demonstrated using murine xenograft models. These results above suggest that hypoxia could activate the cooperation of Bcl-2 and Twist1, Bcl-2 plays an important role in assisting Twist1 nuclear translocation which could change the expression of a wide range of genes and lead to the induction of EMT and VM formation.
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Hypoxia can induce epithelial-mesenchymal transition (EMT).
“Hypoxia can also induce EMT [93,94].”
From The Pathogenesis of Adenomyosis vis-à-vis Endometriosis (2020) · cites this paper as [93]
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- Authors
- Liu, K., Sun, B., Zhao, X., Wang, X., Li, Y., Qiu, Z., Gu, Q., Dong, X., Zhang, Y., Wang, Y., & Zhao, N.
- Affiliations
- Tianjin Medical University (CN)
- Tianjin Medical University General Hospital (CN)
- Tianjin Medical University Cancer Institute and Hospital (CN)
- Corresponding author
- Sun, Baocun
- ORCID
- Venue
- Experimental and Molecular Pathology
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 99
- Issue
- 2
- Pages
- 383-391
- ISSN
- 0014-4800 (ISSN-L)
- OpenAlex
- W1211215382
- Cited by
- 37
- References
- 33
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 6 · 2020: 4 · 2019: 8 · 2018: 1 · 2017: 3 · 2016: 2
- FWCI
- 0.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental and Molecular Pathology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (No. 81230050, No. 81172046, No. 81173091)
- Tianjin Natural Science Foundation (No. 12JCZDJC23600)
- Natural Science Foundation of Tianjin Education Commission (No. 20120103)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- hypoxia, epithelial-mesenchymal transition, vasculogenic mimicry, Bcl-2, TWIST1, hepatocellular carcinoma, tumor progression, tumor microenvironment
- MeSH terms
- Animals, Hypoxia, Cell Movement, Fluorescent Antibody Technique, Carcinoma, Hepatocellular, Humans, Immunoenzyme Techniques, Liver Neoplasms, Male, Mice, Inbred BALB C, Mice, Nude, Neovascularization, Pathologic, Nuclear Proteins, Tumor Cells, Cultured, Wound Healing, Blotting, Western, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Xenograft Model Antitumor Assays, Cell Proliferation, Mice, Twist-Related Protein 1, Epithelial-Mesenchymal Transition
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