Cited by 37Cancer, Hypoxia, and MetabolismCancer Cells and MetastasisHepatocellular Carcinoma Treatment and Prognosis

HIFs enhance the migratory and neoplastic capacities of hepatocellular carcinoma cells by promoting EMT

Liu, Yang, Liu, Yawei, Yan, Xiaolu, Xu, Yuan, Luo, Fei, Ye, Jing, Yan, Han, Yang, Xiaojun +3 more·2014·Tumor Biology

Abstract

Hepatocellular carcinoma (HCC) is one of the most fatal cancers. Although the involvement of the epithelial-to-mesenchymal transition (EMT) in HCC progression is established, the mechanisms modulating this phenomenon remain unclear. Here, we demonstrate that hypoxia-inducible factors (HIFs), HIF-1α and HIF-2α, modulate the EMT through Twist1, a regulator of the EMT. The levels of HIF-1α and HIF-2α in HCC tissues were higher than those in matched, non-tumor surrounding tissues. In HCC samples, the levels of HIF-1α and HIF-2α negatively correlated with the levels of E-cadherin but positively correlated with the levels of vimentin. In highly metastatic MHCC97H cells, the levels of HIF-1α, HIF-2α, and Twist1 were higher than those in weakly metastatic HepG2 cells. In HepG2 cells, over-expression of HIFs enhanced levels of Twist1 and the EMT, which elevated the migratory and neoplastic capacities of cells. For MHCC97H cells, inhibition of HIFs reduced Twist1 levels and the EMT, which reduced their migratory and neoplastic capacity. Thus, the promotion of EMT by HIFs via Twist1 enhanced the migration and neoplastic capacities of HCC cells.

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Crossref · 10.1007/s13277-014-2056-0

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  • Hypoxia or overexpression of HIF is sufficient to induce EMT and invasion in multiple cell types.

    “Hypoxia or overexpression of HIF is sufficient to induce EMT and invasion in multiple cell types”

    From Hypoxic control of metastasis (2016) · cites this paper as [71]

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Authors
Liu, Y., Liu, Y., Yan, X., Xu, Y., Luo, F., Ye, J., Yan, H., Yang, X., Huang, X., Zhang, J., & Ji, G.
Affiliations
  • Nanjing Medical University (CN)
  • Second Affiliated Hospital of Nanjing Medical University (CN)
Corresponding author
  • Zhang, Jianping
  • Ji, Guozhong
Venue
Tumor Biology
Published
2014-05-20
Volume
35
Issue
8
Pages
8103-8114
ISSN
  • 1010-4283 (ISSN-L)
  • 1423-0380
OpenAlex
W2121263831
Cited by
37
References
36
Citations by year
2026: 1 · 2025: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 6 · 2017: 6 · 2016: 5 · 2015: 4 · 2014: 2
FWCI
1.81
Type
journal article
Language
en
Open access
closed
Locations
  • Tumor Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of Alabama at Birmingham
  • Government of Jiangsu Province
  • Nanjing Medical University
  • Nanjing University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
Keywords
hepatocellular carcinoma, hypoxia-inducible factor, HIF-1α, HIF-2α, epithelial-mesenchymal transition, TWIST1, cell migration, metastasis, E-cadherin, vimentin, MHCC97H cells, HepG2 cells
MeSH terms
Zinc Finger E-box-Binding Homeobox 1, Endothelial PAS Domain-Containing Protein 1, Cell Movement, Cells, Cultured, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Nuclear Proteins, Transcription Factors, Homeodomain Proteins, Basic Helix-Loop-Helix Proteins, Hypoxia-Inducible Factor 1, alpha Subunit, Twist-Related Protein 1, Epithelial-Mesenchymal Transition

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