title: Expression of WNT genes in cervical cancer-derived cells: Implication of WNT7A in cell proliferation and migration.
abstract: According to the multifactorial model of cervical cancer (CC) causation, it is now recognized that other modifications, in addition to Human papillomavirus (HPV) infection, are necessary for the development of this neoplasia. Among these, it has been proposed that a dysregulation of the WNT pathway might favor malignant progression of HPV-immortalized keratinocytes. The aim of this study was to identify components of the WNT pathway differentially expressed in CC vs. non-tumorigenic, but immortalized human keratinocytes. Interestingly, WNT7A expression was found strongly downregulated in cell lines and biopsies derived from CC. Restoration of WNT7A in CC-derived cell lines using a lentiviral gene delivery system or after adding a recombinant human protein decreases cell proliferation. Likewise, WNT7A silencing in non-tumorigenic cells markedly accelerates proliferation. Decreased WNT7A expression was due to hypermethylation at particular CpG sites. To our knowledge, this is the first study reporting reduced WNT7A levels in CC-derived cells and that ectopic WNT7A restoration negatively affects cell proliferation and migration.
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO)-Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico; Programa de Doctorado en Ciencias Biomédica, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara, Jalisco, Mexico. Electronic address: mrsolano84@gmail.com.
authors.forename: Moisés
authors.initials: M
authors.lastname: Ramos-Solano
authors.affiliation: Department of Molecular Ecology, Max Planck Institute for Chemical Ecology, 07745 Jena, Germany. Electronic address: imezacanales@ice.mpg.de.
authors.forename: Ivan D
authors.initials: ID
authors.lastname: Meza-Canales
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO)-Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico; Programa de Doctorado en Ciencias Biomédica, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara, Jalisco, Mexico. Electronic address: torres_reyes_88@hotmail.com.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Torres-Reyes
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO)-Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico; Programa de Doctorado en Ciencias Biomédica, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara, Jalisco, Mexico. Electronic address: monse_belan@hotmail.com.
authors.forename: Monserrat
authors.initials: M
authors.lastname: Alvarez-Zavala
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO)-Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico; Programa de Doctorado en Ciencias Biomédica, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara, Jalisco, Mexico. Electronic address: lilit1585@hotmail.com.
authors.forename: Liliana
authors.initials: L
authors.lastname: Alvarado-Ruíz
authors.affiliation: Division of Viral Transformation Mechanisms, German Cancer Research Center, Heidelberg, Germany. Electronic address: b.orozco@dkfz-heidelberg.de.
authors.forename: Bladimiro
authors.initials: B
authors.lastname: Rincon-Orozco
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO)-Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico. Electronic address: maye_999@hotmail.com.
authors.forename: Mariel
authors.initials: M
authors.lastname: Garcia-Chagollan
authors.affiliation: División de Genética, CIBO-IMSS, Guadalajara, Jalisco, Mexico. Electronic address: bereniceqfb@hotmail.com.
authors.forename: Alejandra B
authors.initials: AB
authors.lastname: Ochoa-Hernández
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO)-Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico. Electronic address: pablolazareno@gmail.com.
authors.forename: Pablo C
authors.initials: PC
authors.lastname: Ortiz-Lazareno
authors.affiliation: Division of Viral Transformation Mechanisms, German Cancer Research Center, Heidelberg, Germany. Electronic address: f.roesl@dkfz-heidelberg.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Rösl
authors.affiliation: Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Mexico City, Mexico. Electronic address: vidal@cinvestav.mx.
authors.forename: Patricio
authors.initials: P
authors.lastname: Gariglio
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO)-Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico. Electronic address: lfjave@yahoo.com.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Jave-Suárez
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO)-Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico. Electronic address: adry.aguilar.lemarroy@gmail.com.
authors.forename: Adriana
authors.initials: A
authors.lastname: Aguilar-Lemarroy
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D017077:Culture Media, Conditioned / Q000494:pharmacology; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering; D011994:Recombinant Proteins / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism; D051153:Wnt Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D017077:Culture Media, Conditioned; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C092778:WNT7A protein, human; D051153:Wnt Proteins
keywords: Cancer; Carcinogenesis; Cervical cancer; HPV; WNT signaling; WNT7A