Tumor Biology

, Volume 35, Issue 8, pp 8103–8114 | Cite as

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

  • Yang Liu
  • Yawei Liu
  • Xiaolu Yan
  • Yuan Xu
  • Fei Luo
  • Jing Ye
  • Han Yan
  • Xiaojun Yang
  • Xiaodan Huang
  • Jianping Zhang
  • Guozhong Ji
Research Article


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.


Hepatocellular carcinoma (HCC) Hypoxia-inducible factors (HIFs) Epithelial–mesenchymal transition (EMT) Migration Neoplastic capacities 



The authors wish to thank Donald L. Hill (University of Alabama at Birmingham, USA) for editing. This work was supported by the Natural Science Foundations of China (81272713 and 81100253), Natural Science Foundations of Jiangsu Province (JS20130508), and a Project Funded by Nanjing Medical University (2011NJMU244).

Conflict of interest


Supplementary material

13277_2014_2056_MOESM1_ESM.doc (398 kb)
ESM 1 (DOC 398 kb)
13277_2014_2056_MOESM2_ESM.doc (29 kb)
Table S1 (DOC 29 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Yang Liu
    • 1
  • Yawei Liu
    • 2
  • Xiaolu Yan
    • 3
  • Yuan Xu
    • 4
  • Fei Luo
    • 4
  • Jing Ye
    • 2
  • Han Yan
    • 2
  • Xiaojun Yang
    • 2
  • Xiaodan Huang
    • 3
  • Jianping Zhang
    • 2
  • Guozhong Ji
    • 3
  1. 1.The First Clinic Medical CollegeNanjing Medical UniversityNanjingPeople’s Republic of China
  2. 2.Department of General Surgery, the Second Affiliated HospitalNanjing Medical UniversityNanjingPeople’s Republic of China
  3. 3.Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, the Second Affiliated HospitalNanjing Medical UniversityNanjingPeople’s Republic of China
  4. 4.School of Public HealthNanjing Medical UniversityNanjingPeople’s Republic of China

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