1. Expression of WNT genes in cervical cancer-derived cells: Implication of WNT7A in cell proliferation and migration.
- Author
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Ramos-Solano M, Meza-Canales ID, Torres-Reyes LA, Alvarez-Zavala M, Alvarado-Ruíz L, Rincon-Orozco B, Garcia-Chagollan M, Ochoa-Hernández AB, Ortiz-Lazareno PC, Rösl F, Gariglio P, Jave-Suárez LF, and Aguilar-Lemarroy A
- Subjects
- Cell Line, Tumor, Cell Movement drug effects, Cell Proliferation drug effects, Cell Survival drug effects, Cell Survival genetics, Culture Media, Conditioned pharmacology, Female, HeLa Cells, Humans, RNA Interference, RNA, Small Interfering, Recombinant Proteins pharmacology, Uterine Cervical Neoplasms metabolism, Wnt Proteins biosynthesis, Wnt Proteins pharmacology, Wnt Signaling Pathway genetics, Cell Movement genetics, Cell Proliferation genetics, DNA Methylation genetics, Uterine Cervical Neoplasms genetics, Wnt Proteins genetics
- 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., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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