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

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...

Full description

Saved in:
Bibliographic Details
Published in:Experimental cell research 2015-07, Vol.335 (1), p.39-50
Main Authors: Ramos-Solano, Moisés, Meza-Canales, Ivan D., Torres-Reyes, Luis A., Alvarez-Zavala, Monserrat, Alvarado-Ruíz, Liliana, Rincon-Orozco, Bladimiro, Garcia-Chagollan, Mariel, Ochoa-Hernández, Alejandra B., Ortiz-Lazareno, Pablo C., Rösl, Frank, Gariglio, Patricio, Jave-Suárez, Luis F., Aguilar-Lemarroy, Adriana
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
BIOPSY
Cancer
CARCINOGENESIS
Cell adhesion & migration
Cell growth
Cell Line, Tumor
Cell Movement - drug effects
Cell Movement - genetics
CELL PROLIFERATION
Cell Proliferation - drug effects
Cell Proliferation - genetics
Cell Survival - drug effects
Cell Survival - genetics
Cervical cancer
Culture Media, Conditioned - pharmacology
DNA Methylation - genetics
Female
Gene expression
GENES
HeLa Cells
HPV
Humans
MIGRATION
NEOPLASMS
PROTEINS
Recombinant Proteins - pharmacology
RNA Interference
RNA, Small Interfering
Signal transduction
Uterine Cervical Neoplasms - genetics
Uterine Cervical Neoplasms - metabolism
Wnt Proteins - biosynthesis
Wnt Proteins - genetics
Wnt Proteins - pharmacology
WNT signaling
Wnt Signaling Pathway - genetics
WNT7A
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. •WNT7A is expressed in normal keratinocytes or cervical cells without lesion.•WNT7A is significantly reduced in cervical cancer-derived cells.•Restoration of WNT7A expression in HeLa decreases proliferation and cell migration.•Silencing of WNT7A in HaCaT induces an increased proliferation and migration rate.•Decreased WNT7A expression in this model is due to hypermethylation.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2015.05.001