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.