Galectin-8 induces partial epithelial-mesenchymal transition with invasive tumorigenic capabilities involving a FAK/EGFR/proteasome pathway in Madin-Darby canine kidney cells.

Autor:	Oyanadel C; Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina, Universidad San Sebastián, 7510156 Santiago, Chile.; Fundación Ciencia y Vida, 7780272 Santiago, Chile., Holmes C; Center for Aging and Regeneration (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8330023 Santiago, Chile., Pardo E; Center for Aging and Regeneration (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8330023 Santiago, Chile., Retamal C; Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina, Universidad San Sebastián, 7510156 Santiago, Chile.; Center for Aging and Regeneration (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8330023 Santiago, Chile., Shaughnessy R; Center for Aging and Regeneration (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8330023 Santiago, Chile., Smith P; Unidad de Odontología, Pontificia Universidad Católica de Chile, 8330023 Santiago, Chile., Cortés P; Center for Aging and Regeneration (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8330023 Santiago, Chile., Bravo-Zehnder M; Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina, Universidad San Sebastián, 7510156 Santiago, Chile.; Center for Aging and Regeneration (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8330023 Santiago, Chile., Metz C; Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina, Universidad San Sebastián, 7510156 Santiago, Chile.; Center for Aging and Regeneration (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8330023 Santiago, Chile., Feuerhake T; Center for Aging and Regeneration (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8330023 Santiago, Chile., Romero D 5th; Departamento de Patología, Pontificia Universidad Católica de Chile, 8330023 Santiago, Chile., Roa JC; Departamento de Patología, Pontificia Universidad Católica de Chile, 8330023 Santiago, Chile., Montecinos V; Departamento de Hematología y Oncología, Facultad de Medicina, Pontificia Universidad Católica de Chile, 8330023 Santiago, Chile., Soza A; Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina, Universidad San Sebastián, 7510156 Santiago, Chile agonzara@uss.cl andrea.soza@uss.cl.; Center for Aging and Regeneration (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8330023 Santiago, Chile., González A; Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina, Universidad San Sebastián, 7510156 Santiago, Chile agonzara@uss.cl andrea.soza@uss.cl.; Center for Aging and Regeneration (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8330023 Santiago, Chile.
Jazyk:	angličtina
Zdroj:	Molecular biology of the cell [Mol Biol Cell] 2018 Mar 01; Vol. 29 (5), pp. 557-574. Date of Electronic Publication: 2018 Jan 03.
DOI:	10.1091/mbc.E16-05-0301
Abstrakt:	Epithelial cells can acquire invasive and tumorigenic capabilities through epithelial-mesenchymal-transition (EMT). The glycan-binding protein galectin-8 (Gal-8) activates selective β1-integrins involved in EMT and is overexpressed by certain carcinomas. Here we show that Gal-8 overexpression or exogenous addition promotes proliferation, migration, and invasion in nontumoral Madin-Darby canine kidney (MDCK) cells, involving focal-adhesion kinase (FAK)-mediated transactivation of the epidermal growth factor receptor (EGFR), likely triggered by α5β1integrin binding. Under subconfluent conditions, Gal-8-overexpressing MDCK cells (MDCK-Gal-8 H ) display hallmarks of EMT, including decreased E-cadherin and up-regulated expression of vimentin, fibronectin, and Snail, as well as increased β-catenin activity. Changes related to migration/invasion included higher expression of α5β1 integrin, extracellular matrix-degrading MMP13 and urokinase plasminogen activator/urokinase plasminogen activator receptor (uPA/uPAR) protease systems. Gal-8-stimulated FAK/EGFR pathway leads to proteasome overactivity characteristic of cancer cells. Yet MDCK-Gal-8 H cells still develop apical/basolateral polarity reverting EMT markers and proteasome activity under confluence. This is due to the opposite segregation of Gal-8 secretion (apical) and β1-integrins distribution (basolateral). Strikingly, MDCK-Gal-8 H cells acquired tumorigenic potential, as reflected in anchorage-independent growth in soft agar and tumor generation in immunodeficient NSG mice. Therefore, Gal-8 can promote oncogenic-like transformation of epithelial cells through partial and reversible EMT, accompanied by higher proliferation, migration/invasion, and tumorigenic properties. (© 2018 Oyanadel et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu