title: Emodin represses TWIST1-induced epithelial-mesenchymal transitions in head and neck squamous cell carcinoma cells by inhibiting the β-catenin and Akt pathways.
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.
authors.affiliation: Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan; Department of Health and Nutrition Biotechnology, College of Health Science, Asia University, Taichung, Taiwan. Electronic address: tdway@mail.cmu.edu.tw.
authors.forename: Tzong-Der
authors.initials: TD
authors.lastname: Way
authors.affiliation: Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan.
authors.forename: Jhen-Ting
authors.initials: JT
authors.lastname: Huang
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Chou
authors.affiliation: Taiwan Advance Biopharm, New Taipei City, Taiwan; Graduate School of Biotechnology, Hung-Kuang University, Taichung, Taiwan.
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Huang
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Hematology-Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Muh-Hwa
authors.initials: MH
authors.lastname: Yang
authors.affiliation: Department of Food Science, Rutgers University, New Brunswick, NJ, USA.
authors.forename: Chi-Tang
authors.initials: CT
authors.lastname: Ho
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D004642:Emodin / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D005260:Female; D057809:HEK293 Cells; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018613:Microscopy, Confocal; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D014407:Tumor Cells, Cultured; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D051176:beta Catenin; D051057:Proto-Oncogene Proteins c-akt; D004642:Emodin
keywords: Emodin; Epithelial–mesenchymal transition; Head and neck squamous cell carcinoma; TWIST1