FXYD5/Dysadherin, a Biomarker of Endometrial Cancer Myometrial Invasion and Aggressiveness : Its Relationship With TGF-β1 and NF-κB Pathways
Besso, María josé (Laboratorio de Estudios de la Interacción Celular en Reproducción y Cáncer. Instituto de Biología y Medicina Experimental (IBYME; CONICET-FIBYME))
Rosso, M. (Laboratorio de Estudios de la Interacción Celular en Reproducción y Cáncer. Instituto de Biología y Medicina Experimental (IBYME; CONICET-FIBYME))
Lapyckyj, L. (Laboratorio de Estudios de la Interacción Celular en Reproducción y Cáncer. Instituto de Biología y Medicina Experimental (IBYME; CONICET-FIBYME))
Moiola, Cristian Pablo (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Matos, M. L. (Laboratorio de Estudios de la Interacción Celular en Reproducción y Cáncer. Instituto de Biología y Medicina Experimental (IBYME; CONICET-FIBYME))
Mercogliano, M. F. (Instituto de Biología y Medicina Experimental (Buenos Aires, Argentina))
Schillaci, R. (Instituto de Biología y Medicina Experimental (Buenos Aires, Argentina))
Reventós Puigjaner, Jaume (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Colás Ortega, Eva (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Gil-Moreno, Antonio 1965- (Hospital Universitari Vall d'Hebron)
Wernicke, A. (Hospital Italiano de Buenos Aires (Argentina))
Orti, R. (Hospital Italiano de Buenos Aires (Argentina))
Vazquez-Levin, M. H. (Laboratorio de Estudios de la Interacción Celular en Reproducción y Cáncer. Instituto de Biología y Medicina Experimental (IBYME; CONICET-FIBYME))
Universitat Autònoma de Barcelona

Data:	2019
Resum:	Objective: Endometrial cancer (EC) is the second most common gynecological cancer worldwide. Myometrial invasion (MI) is a key event in EC dissemination. This study aimed to evaluate FXYD5/dysadherin (FXYD5/Dys) expression in EC tissue and uterine aspirate (UA) biopsies and to assess molecular/functional changes associated with its expression in cellular models. Methods: FXYD5/Dys messenger RNA (mRNA) levels were determined in EC tissue and UA biopsies. FXYD5/Dys expression was evaluated in EC RNAseq data from The Cancer Genome Atlas (TCGA) and GENEVESTIGATOR tools. FXYD5/Dys impact on E-cadherin expression and cell behavior was assessed in EC Hec1a cells treated with transforming growth factor (TGF)-β1, stably transfected with ETV5, and transiently transfected with FXYD5/Dys small interfering RNA (siRNA) or pcDNA3-FXYD5/Dys plasmid. Results: FXYD5/Dys was associated with EC aggressiveness, finding high mRNA levels in tumors depicting MI > 50%, Grade 3, and intermediate/high risk of recurrence. FXYD5/Dys was highly expressed at the tumor invasive front compared to the superficial area. Most results were recapitulated in UA biopsies. FXYD5/Dys modulation in Hec1a cells altered cell migration/adhesion and E-cadherin expression. TGF-β1 treatment of Hec1a cells induced FXYD5/Dys expression. TCGA-UCEC RNAseq analysis revealed a positive correlation between FXYD5/Dys, TGF-β1, and plasminogen activator inhibitor (PAI)-1 mRNA levels. FXYD5/Dys induced nuclear factor (NF)-κB pathway activation in Hec1a cells. FXYD5/Dys mRNA levels positively correlated with transcriptional activation of NF-κB p65-regulated genes. Survival analysis revealed patient segregation into low- and high-risk groups, the latter depicting the highest FXYD5/Dys, PAI-1, tumor necrosis factor (TNF)-α, and TGF-β1 mRNA levels and shorter survival rates. Conclusion: FXYD5/Dys is a novel biomarker of EC progression related to TGF-β1 and NF-κB pathways that collectively promote tumor dissemination and result in poor patient prognosis.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	CCL-2 ; E-cadherin ; FXYD5 ; NF-κB ; TGF-β1 ; Dysadherin ; Endometrial cancer
Publicat a:	Frontiers in Oncology, Vol. 9 (june 2019) , p. 1306, ISSN 2234-943X

DOI: 10.3389/fonc.2019.01306
PMID: 31867269

0 p, 1.1 MB

El registre apareix a les col·leccions:
Articles > Articles de recerca
Articles > Articles publicats