title: Colon cancer cell invasion is promoted by protein kinase CK2 through increase of endothelin-converting enzyme-1c protein stability.
abstract: Endothelin-converting enzyme-1c (ECE-1c) is a membrane metalloprotease involved in endothelin-1 synthesis, which has been shown in vitro to have a role in breast, ovary and prostate cancer cell invasion. N-terminal end of ECE-1c displays three putative phosphorylation sites for the protein kinase CK2. We studied whether CK2 phosphorylates N-terminal end of ECE-1c as well as whether this has a role in migration and invasion of colon cancer cells. CK2 phosphorylated the N-terminal end of ECE-1c and this was precluded upon inhibition of CK2. Inhibition also led to diminished protein levels of both endogen ECE-1 or GFP-fused N-terminal end of ECE-1c in 293T embryonic and DLD-1 colon cancer cells, which highlighted the importance of this motif on UPS-dependent ECE-1c degradation. Full-length ECE-1c mutants designed either to mimic or abrogate CK2-phosphorylation displayed increased or decreased migration/invasion of colon cancer cells, respectively. Moreover, ECE-1c overexpression or its silencing with a siRNA led to increased or diminished cell migration/invasion, respectively. Altogether, these data show that CK2-increased ECE-1c protein stability is related to augmented migration and invasion of colon cancer cells, shedding light on a novel mechanism by which CK2 may promote malignant progression of this disease.
authors.affiliation: Cell Transformation Laboratory, Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Niechi
authors.affiliation: Cell Transformation Laboratory, Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Silva
authors.affiliation: Cell Transformation Laboratory, Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Cabello
authors.affiliation: Cell Transformation Laboratory, Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Hernan
authors.initials: H
authors.lastname: Huerta
authors.affiliation: Cell Transformation Laboratory, Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Valentina
authors.initials: V
authors.lastname: Carrasco
authors.affiliation: Cell Transformation Laboratory, Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Paulina
authors.initials: P
authors.lastname: Villar
authors.affiliation: Cell Transformation Laboratory, Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Luis Rodrigo
authors.initials: LR
authors.lastname: Cataldo
authors.affiliation: ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Katherine
authors.initials: K
authors.lastname: Marcelain
authors.affiliation: ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Armisen
authors.affiliation: Fundacion Ciencia y Vida, Santiago, Chile.
authors.forename: Manuel
authors.initials: M
authors.lastname: Varas-Godoy
authors.affiliation: Department of Anatomopathology, HCUCH, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Cristina
authors.initials: C
authors.lastname: Fernandez
authors.affiliation: Cell Transformation Laboratory, Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.|ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Julio C
authors.initials: JC
authors.lastname: Tapia
mesh_terms: D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D015153:Blotting, Western; D047390:Casein Kinase II / Q000378:metabolism; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D003110:Colonic Neoplasms / Q000473:pathology*; D000072396:Endothelin-Converting Enzymes; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism*; D018613:Microscopy, Confocal; D009361:Neoplasm Invasiveness / Q000473:pathology*; D055550:Protein Stability; D034741:RNA, Small Interfering; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; C570325:CSNK2A1 protein, human; D047390:Casein Kinase II; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes
keywords: CK2; ECE-1; colon cancer; endothelin; metastasis