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dc.contributor.author
Matos, María Laura
dc.contributor.author
Lapyckyj, Lara
dc.contributor.author
Rosso, Marina
dc.contributor.author
Besso, María José
dc.contributor.author
Mencucci, Maria Victoria
dc.contributor.author
Marin Briggiler, Clara Isabel
dc.contributor.author
Giustina, Silvina
dc.contributor.author
Furlong, Laura Ines
dc.contributor.author
Vazquez, Monica Hebe
dc.date.available
2017-09-18T18:57:38Z
dc.date.issued
2016-12
dc.identifier.citation
Matos, María Laura; Lapyckyj, Lara; Rosso, Marina; Besso, María José; Mencucci, Maria Victoria; et al.; Identification of a novel human E-Cadherin splice variant andassessment of its effects upon EMT-related events; Wiley; Journal of Cellular Physiology; 232; 6; 12-2016; 1368-1386
dc.identifier.issn
0021-9541
dc.identifier.uri
http://hdl.handle.net/11336/24478
dc.description.abstract
Epithelial Cadherin (E-cadherin) is involved in calcium-dependent cell-cell adhesion and signal transduction. The E-cadherin decrease/loss is a hallmark of Epithelial to Mesenchymal Transition (EMT), a key event in tumor progression. The underlying molecular mechanisms that trigger E-cadherin loss and consequent EMT have not been completely elucidated. This study reports the identification of a novel human E-cadherin variant mRNA produced by alternative splicing. A bioinformatics evaluation of the novel mRNA sequence and biochemical verifications suggest its regulation by Nonsense-Mediated mRNA Decay (NMD). The novel E-cadherin variant was detected in 29/42 (69%) human tumor cell lines, expressed at variable levels (E-cadherin variant expression relative to the wild type mRNA = 0.05-11.6%). Stable transfection of the novel E-cadherin variant in MCF-7 cells (MCF7Ecadvar) resulted in downregulation of wild type E-cadherin expression (transcript/protein) and EMT-related changes, among them acquisition of a fibroblastic-like cell phenotype, increased expression of Twist, Snail, Zeb1, and Slug transcriptional repressors and decreased expression of ESRP1 and ESRP2 RNA binding proteins. Moreover, loss of cytokeratins and gain of vimentin, N-cadherin and Dysadherin/FXYD5 proteins was observed. Dramatic changes in cell behavior were found in MCF7Ecadvar, as judged by the decreased cell-cell adhesion (Hanging-drop assay), increased cell motility (Wound Healing) and increased cell migration (Transwell) and invasion (Transwell w/Matrigel). Some changes were found in MCF-7 cells incubated with culture medium supplemented with conditioned medium from HEK-293 cells transfected with the E-cadherin variant mRNA. Further characterization of the novel E-cadherin variant will help understanding the molecular basis of tumor progression and improve cancer diagnosis.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Wiley
dc.rights
info:eu-repo/semantics/embargoedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Cancer
dc.subject
Epithelial Cadherin
dc.subject
Epithelial to Mesenchymal Transition
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Alternative Splicing
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Bioquímica y Biología Molecular
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
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Patología
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Identification of a novel human E-Cadherin splice variant andassessment of its effects upon EMT-related events
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-09-08T20:19:16Z
dc.identifier.eissn
1097-4652
dc.journal.volume
232
dc.journal.number
6
dc.journal.pagination
1368-1386
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Hoboken
dc.conicet.avisoEditorial
Esta es la versión revisada por pares del siguiente artículo Matos, María Laura; Lapyckyj, Lara; Rosso, Marina; Besso, María José; Mencucci, Maria Victoria; et al.; Identification of a Novel Human E-Cadherin Splice Variant and Assessment of its Effects upon EMT-Related Events; Wiley-liss, Div John Wiley & Sons Inc; Journal of Cellular Physiology; 232; 6; 6-2017; 1368-1386 que se ha publicado en forma final en http://dx.doi.org/10.1002/jcp.25622 Este artículo puede ser utilizado con fines no comerciales de acuerdo con Wiley Terms y condiciones para el auto-archivado.
dc.description.fil
Fil: Matos, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.description.fil
Fil: Lapyckyj, Lara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.description.fil
Fil: Rosso, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.description.fil
Fil: Besso, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.description.fil
Fil: Mencucci, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.description.fil
Fil: Marin Briggiler, Clara Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.description.fil
Fil: Giustina, Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.description.fil
Fil: Furlong, Laura Ines. Universitat Pompeu Fabra; España
dc.description.fil
Fil: Vazquez, Monica Hebe. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.journal.title
Journal of Cellular Physiology
dc.rights.embargoDate
2018-01-01
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1002/jcp.25622
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/jcp.25622/abstract


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