Open Access

Wnt/β‑catenin pathway activation and silencing of the APC gene in HPV‑positive human cervical cancer‑derived cells

  • Authors:
    • Erick Ayala‑Calvillo
    • Luis Humberto Mojica‑Vázquez
    • Alejandro García‑Carrancá
    • Leticia González‑Maya
  • View Affiliations

  • Published online on: October 20, 2017     https://doi.org/10.3892/mmr.2017.7853
  • Pages:200-208
  • Copyright: © Ayala‑Calvillo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although persistent infections with high‑risk human papilloma virus (HPV) constitute the most significant cofactor for the development of cervical cancer, they are insufficient on their own. Mutations or epigenetic inactivation of the tumor suppressor adenomatous polyposis coli (APC), the two acting as prominent oncogenic mechanisms in a number of types of cancer, are frequently associated with aberrant activation of the Wnt/β‑catenin pathway. According to these observations, it was hypothesized that APC alteration may lead to β‑catenin deregulation and the abnormal expression of direct targets of the Wnt pathway in HPV‑infected cervical cancer cells. The present study confirmed that the stabilization of β‑catenin correlates with enhanced transcriptional activity of the β‑catenin/T‑cell factor complex in cervical cancer cell lines. Sequence analysis of the ‘hot‑spot’ in the mutation cluster region did not exhibit genetic alterations that may be associated with APC gene inactivation. In addition, it was identified that there was a good correlation with the hypermethylation status of the APC promoter 1A and the abnormal accumulation of endogenous β‑catenin in cell lines and biopsies infected with HPV16, although not HPV18. Removal of the epigenetic markers led to an increase in APC levels and a reduction of β‑catenin expression in two transcriptional targets of the Wnt pathway: Matrix metalloproteinase‑7 and vascular endothelial growth factor. The present study suggested that the increase in Wnt activity in certain cervical cancer‑derived cells may be associated with an alteration in the methylation status of the APC gene promoter 1A.

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January 2018
Volume 17 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

2016 Impact Factor: 1.692
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APA
Ayala‑Calvillo, E., Mojica‑Vázquez, L.H., García‑Carrancá, A., & González‑Maya, L. (2018). Wnt/β‑catenin pathway activation and silencing of the APC gene in HPV‑positive human cervical cancer‑derived cells. Molecular Medicine Reports, 17, 200-208. https://doi.org/10.3892/mmr.2017.7853
MLA
Ayala‑Calvillo, E., Mojica‑Vázquez, L. H., García‑Carrancá, A., González‑Maya, L."Wnt/β‑catenin pathway activation and silencing of the APC gene in HPV‑positive human cervical cancer‑derived cells". Molecular Medicine Reports 17.1 (2018): 200-208.
Chicago
Ayala‑Calvillo, E., Mojica‑Vázquez, L. H., García‑Carrancá, A., González‑Maya, L."Wnt/β‑catenin pathway activation and silencing of the APC gene in HPV‑positive human cervical cancer‑derived cells". Molecular Medicine Reports 17, no. 1 (2018): 200-208. https://doi.org/10.3892/mmr.2017.7853