title: Transcription factor SPZ1 promotes TWIST-mediated epithelial-mesenchymal transition and oncogenesis in human liver cancer.
abstract: The epithelial-mesenchymal transition (EMT) is an important process in the progression of cancer. However, its occurrence and mechanism of regulation are not fully understood. We propose a regulatory pathway in which spermatogenic leucine zipper 1 (SPZ1) promotes EMT through its transactivating ability in increasing TWIST1 expression. We compared the expression of SPZ1 and TWIST1 in specimens of hepatocarcinoma cells (HCCs) and non-HCCs. Expression of SPZ1 exhibited a tumor-specific expression pattern and a high correlation with patients' survival time, tumor size, tumor number and progression stage. Moreover, forced expression and knockdown of SPZ1 in hepatoma cells showed that SPZ1 was able to regulate the cellular proliferation, invasion, and tumorigenic activity in a TWIST1-dependent manner in vitro and in vivo. These data demonstrate that SPZ1, a newly dscribed molecule, transactivates TWIST1 promoters, and that this SPZ1-TWIST axis mediates EMT signaling and exerts significant regulatory effects on tumor oncogenesis.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: L-T
authors.initials: LT
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Division of Hematology-Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: S-S
authors.initials: SS
authors.lastname: Chiou
authors.affiliation: Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Chai
authors.affiliation: Department of Genome Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: E
authors.initials: E
authors.lastname: Hsi
authors.affiliation: Departments of Pharmacology and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: C-M
authors.initials: CM
authors.lastname: Chiang
authors.affiliation: Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: S-K
authors.initials: SK
authors.lastname: Huang
authors.affiliation: Division of Hepatobiliary Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Surgery, Faculty of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: S-N
authors.initials: SN
authors.lastname: Wang
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Pharmaceutical Science, Tokushima Bunri University, Sanuki, Japan.|Department of Molecular Preventive Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.|Center of Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.|Center for Environmental Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: K K
authors.initials: KK
authors.lastname: Yokoyama
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Center of Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: S-H
authors.initials: SH
authors.lastname: Hsu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000502:physiology*; D063646:Carcinogenesis; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000502:physiology*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D009687:Nuclear Proteins; C481348:SPZ1 protein, human; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1