Emodin represses TWIST1-induced epithelial-mesenchymal transitions in head and neck squamous cell carcinoma cells by inhibiting the β-catenin and Akt pathways

Tzong Der Way, Jhen Ting Huang, Chun Hung Chou, Chi Hung Huang, Muh Hwa Yang, Chi Tang Ho

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Head and neck squamous cell carcinoma (HNSCC) is one of the leading causes of cancer deaths worldwide. In recent studies, a crucial link has been discovered between the acquisition of metastatic traits and tumour-initiating abilities in cancer cells during the epithelial-mesenchymal transition (EMT). Herein, we demonstrated that the ectopic expression of TWIST1, the EMT regulator, in HNSCC FaDu cells triggered EMT and resulted in the acquisition of a mesenchymal phenotype. Moreover, FaDu-pFLAG-TWIST1 cancer cell populations that were induced to EMT displayed an increased proportion of cells with the CD44 marker, which is associated with tumour initiation. Interestingly, we found that emodin treatment reduced the tumour-initiating abilities and inhibited cell migration and invasion in FaDu-pFLAG-TWIST1 cells. Emodin directly inhibited TWIST1 expression, upregulated E-cadherin mRNA and protein expression, and downregulated vimentin mRNA and protein expression. Moreover, we found that emodin inhibited TWIST1 binding to the E-cadherin promoter and repressed E-cadherin transcription activity. We also found that emodin inhibited TWIST1-induced EMT by inhibiting the β-catenin and Akt pathways. More interestingly, emodin significantly inhibited TWIST1-induced invasion in vivo. Therefore, emodin might be applicable to anticancer therapy and could be a potential new therapeutic drug for HNSCC.

Original languageEnglish (US)
Pages (from-to)366-378
Number of pages13
JournalEuropean Journal of Cancer
Volume50
Issue number2
DOIs
StatePublished - Jan 2014

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Keywords

  • Emodin
  • Epithelial-mesenchymal transition
  • Head and neck squamous cell carcinoma
  • TWIST1

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