Colon cancer cell invasion is promoted by protein kinase CK2 through increase of endothelin-converting enzyme-1c protein stability.

Autor:	Niechi I; Cell Transformation Laboratory, Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile., Silva E; Cell Transformation Laboratory, Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile., Cabello P; Cell Transformation Laboratory, Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile., Huerta H; Cell Transformation Laboratory, Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile., Carrasco V; Cell Transformation Laboratory, Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile., Villar P; Cell Transformation Laboratory, Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile., Cataldo LR; Cell Transformation Laboratory, Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile., Marcelain K; ICBM, Faculty of Medicine, University of Chile, Santiago, Chile., Armisen R; ICBM, Faculty of Medicine, University of Chile, Santiago, Chile., Varas-Godoy M; Fundacion Ciencia y Vida, Santiago, Chile., Fernandez C; Department of Anatomopathology, HCUCH, Faculty of Medicine, University of Chile, Santiago, Chile., Tapia JC; 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.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2015 Dec 15; Vol. 6 (40), pp. 42749-60.
DOI:	10.18632/oncotarget.5722
Abstrakt:	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.
Databáze:	MEDLINE
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