Hypoxia promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells via inducing Twist1 expression

Eur Rev Med Pharmacol Sci. 2017 Jul;21(13):3061-3068.

Abstract

Objective: To investigate whether hypoxia microenvironment induced hepatocellular carcinoma cells SMMC-7721 epithelial-mesenchymal transition (EMT) and to explore the underlying molecular mechanism.

Materials and methods: In this study, SMMC-7721 cells were cultured under normoxia and hypoxia conditions, respectively. RT-PCR and Western blot were used to monitor the expression level of EMT-related markers, E-cadherin, and vimentin, as well as hypoxia inducible factor-1α (HIF-1α) and Twist1. Then we performed the transwell invasion assays to detect the ability of cell invasion.

Results: The results demonstrated that hypoxia micro-environment could induce hepatocellular carcinoma cells SMMC-7721 EMT and enhance the cell invasion ability. Furthermore, knockdown of Twist1 by using specific siRNA could reverse hypoxia-induced EMT process.

Conclusions: Hypoxia promotes hepatocellular carcinoma cells SMMC-7721 EMT by upregulating the expression of Twist1.

MeSH terms

  • Antigens, CD
  • Cadherins / genetics
  • Cadherins / metabolism
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Hypoxia*
  • Cell Line, Tumor
  • Cell Movement
  • Epithelial-Mesenchymal Transition / genetics*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Transcriptional Activation
  • Twist-Related Protein 1 / antagonists & inhibitors
  • Twist-Related Protein 1 / genetics
  • Twist-Related Protein 1 / metabolism*
  • Vimentin / genetics
  • Vimentin / metabolism

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • RNA, Small Interfering
  • TWIST1 protein, human
  • Twist-Related Protein 1
  • Vimentin