title: Sciellin mediates mesenchymal-to-epithelial transition in colorectal cancer hepatic metastasis.
abstract: Hepatic metastasis is the major cause of mortality in colorectal cancer (CRC) patients. Using proteomic analysis, we found sciellin (SCEL) to be specifically expressed in hepatic metastatic CRC cell lines. SCEL knockdown increased CRC cell migration and invasion, while overexpression had the opposite effect. SCEL knockdown also caused cancer cells to form more invasive structures within 3D cultures, increased the mesenchymal marker vimentin, and attenuated the epithelial marker E-cadherin. SCEL increased WNT signaling by activating β-catenin and its downstream target c-myc, and activated mesenchymal-to-epithelial transition (MET) through a SCEL-β-catenin-E-cadherin axis. SCEL showed higher expression in late stage primary CRC than in its hepatic metastatic counterpart. SCEL expression is dynamically modulated by TGF-β1 and hypoxia, revealing a plastic MET mechanism for tumor colonization. Intrahepatic injection in immunodeficient mice revealed that SCEL is necessary for metastatic CRC tumor growth in the liver. These results demonstrate that SCEL is a MET inducer dynamically regulated through the metastasis process. They suggest SCEL may be a useful therapeutic target for preventing or eliminating CRC hepatic metastasis.
authors.affiliation: National Applied Research Laboratories, National Laboratory Animal Center, Taipei, Taiwan.
authors.forename: Chuan-Kai
authors.initials: CK
authors.lastname: Chou
authors.affiliation: Superintendent Office, Mackay Memorial Hospital, Taipei, Taiwan.|Department of Medical Laboratory Science and Biotechnology, Yuanpei University, Hsinchu, Taiwan.
authors.forename: Chi-Chen
authors.initials: CC
authors.lastname: Fan
authors.affiliation: Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Pei-Shan
authors.initials: PS
authors.lastname: Lin
authors.affiliation: National Applied Research Laboratories, National Laboratory Animal Center, Taipei, Taiwan.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Liao
authors.affiliation: Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan.
authors.forename: Jia-Chen
authors.initials: JC
authors.lastname: Tung
authors.affiliation: Department of Orthopaedic Surgery, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan.
authors.forename: Chang-Hsun
authors.initials: CH
authors.lastname: Hsieh
authors.affiliation: Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.|Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan.|Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.|Institute of Biochemistry & Molecular Biology, National Yang-Ming University, Taipei, Taiwan.|Department of Chemistry, National Taiwan University, Taipei, Taiwan.|Institute of Atomic & Molecular Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chung-Hsuan
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.|Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan.
authors.forename: Wei-Chao
authors.initials: WC
authors.lastname: Chang
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D054338:Cell Transdifferentiation / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis
chemical_list: D002352:Carrier Proteins; C111281:SCEL protein, human
keywords: SCEL; colorectal cancer; hepatic metastasis; mesenchymal-to-epithelial transition