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

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dc.contributor.authorOyanadel, Claudia
dc.contributor.authorHolmes, Christopher
dc.contributor.authorPardo, Evelyn
dc.contributor.authorRetamal, Claudio
dc.contributor.authorShaughnessy, Ronan
dc.contributor.authorSmith, Patricio
dc.contributor.authorCortes, Priscilla
dc.contributor.authorBravo-Zehnder, Marcela
dc.contributor.authorMetz, Claudia
dc.contributor.authorFeuerhake, Teo
dc.contributor.authorRomero, Diego, V
dc.contributor.authorCarlos Roa, Juan
dc.contributor.authorMontecinos, Viviana
dc.contributor.authorSoza, Andrea
dc.contributor.authorGonzalez, Alfonso
dc.date.accessioned2025-01-23T21:23:05Z
dc.date.available2025-01-23T21:23:05Z
dc.date.issued2018
dc.description.abstractEpithelial cells can acquire invasive and tumorigenic capabilities through epithelial-mesenchymal- transition (EMT). The glycan-binding protein galectin-8 (Gal-8) activates selective beta 1-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 alpha 5 beta 1 integrin 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 beta-catenin activity. Changes related to migration/invasion included higher expression of alpha 5 beta 1 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-8H 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 beta 1-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.
dc.fuente.origenWOS
dc.identifier.doi10.1091/mbc.E16-05-0301
dc.identifier.eissn1939-4586
dc.identifier.issn1059-1524
dc.identifier.urihttps://doi.org/10.1091/mbc.E16-05-0301
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/101272
dc.identifier.wosidWOS:000426219300004
dc.issue.numero5
dc.language.isoen
dc.pagina.final574
dc.pagina.inicio557
dc.revistaMolecular biology of the cell
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleGalectin-8 induces partial epithelial-mesenchymal transition with invasive tumorigenic capabilities involving a FAK/EGFR/proteasome pathway in Madin-Darby canine kidney cells
dc.typeartículo
dc.volumen29
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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