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Exp Cell Res. 2015 Jul 1;335(1):39-50. doi: 10.1016/j.yexcr.2015.05.001. Epub 2015 May 12.

Expression of WNT genes in cervical cancer-derived cells: Implication of WNT7A in cell proliferation and migration.

Author information

1
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.
2
Department of Molecular Ecology, Max Planck Institute for Chemical Ecology, 07745 Jena, Germany. Electronic address: imezacanales@ice.mpg.de.
3
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.
4
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.
5
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.
6
Division of Viral Transformation Mechanisms, German Cancer Research Center, Heidelberg, Germany. Electronic address: b.orozco@dkfz-heidelberg.de.
7
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.
8
División de Genética, CIBO-IMSS, Guadalajara, Jalisco, Mexico. Electronic address: bereniceqfb@hotmail.com.
9
División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO)-Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico. Electronic address: pablolazareno@gmail.com.
10
Division of Viral Transformation Mechanisms, German Cancer Research Center, Heidelberg, Germany. Electronic address: f.roesl@dkfz-heidelberg.de.
11
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.
12
División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO)-Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico. Electronic address: lfjave@yahoo.com.
13
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.

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.

KEYWORDS:

Cancer; Carcinogenesis; Cervical cancer; HPV; WNT signaling; WNT7A

PMID:
25978974
DOI:
10.1016/j.yexcr.2015.05.001
[Indexed for MEDLINE]

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