Down-regulation of canonical and up-regulation of non-canonical Wnt signalling in the carcinogenic process of squamous cell lung carcinoma

Domokos Bartis; Veronika Csongei; Alexander Weich; Edit Kiss; Szilvia Barko; Tamas Kovacs; Monika Avdicevic; Vijay K D'Souza; Judit Rapp; Krisztian Kvell; Laszlo Jakab; Miklos Nyitrai; Tamas F Molnar; David R Thickett; Terezia Laszlo; Judit E Pongracz

doi:10.1371/journal.pone.0057393

Down-regulation of canonical and up-regulation of non-canonical Wnt signalling in the carcinogenic process of squamous cell lung carcinoma

PLoS One. 2013;8(3):e57393. doi: 10.1371/journal.pone.0057393. Epub 2013 Mar 7.

Authors

Domokos Bartis¹, Veronika Csongei, Alexander Weich, Edit Kiss, Szilvia Barko, Tamas Kovacs, Monika Avdicevic, Vijay K D'Souza, Judit Rapp, Krisztian Kvell, Laszlo Jakab, Miklos Nyitrai, Tamas F Molnar, David R Thickett, Terezia Laszlo, Judit E Pongracz

Affiliation

¹ Department of Medical Biotechnology, Institute of Immunology and Biotechnology, Medical School, University of Pecs, Pecs, Hungary.

Abstract

The majority of lung cancers (LC) belong to the non-small cell lung carcinoma (NSCLC) type. The two main NSCLC sub-types, namely adenocarcinoma (AC) and squamous cell carcinoma (SCC), respond differently to therapy. Whereas the link between cigarette smoke and lung cancer risk is well established, the relevance of non-canonical Wnt pathway up-regulation detected in SCC remains poorly understood. The present study was undertaken to investigate further the molecular events in canonical and non-canonical Wnt signalling during SCC development. A total of 20 SCC and AC samples with matched non-cancerous controls were obtained after surgery. TaqMan array analysis confirmed up-regulation of non-canonical Wnt5a and Wnt11 and identified down-regulation of canonical Wnt signalling in SCC samples. The molecular changes were tested in primary small airway epithelial cells (SAEC) and various lung cancer cell lines (e.g. A549, H157, etc). Our studies identified Wnt11 and Wnt5a as regulators of cadherin expression and potentiated relocation of β-catenin to the nucleus as an important step in decreased cellular adhesion. The presented data identifies additional details in the regulation of SCC that can aid identification of therapeutic drug targets in the future.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Squamous Cell / genetics
Carcinoma, Squamous Cell / metabolism*
Cell Line, Tumor
Cell Transformation, Neoplastic / metabolism*
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms / genetics
Lung Neoplasms / metabolism*
Protein Transport
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism
Wnt Proteins / genetics
Wnt Proteins / metabolism
Wnt Signaling Pathway*
Wnt-5a Protein
beta Catenin / metabolism

Substances

Proto-Oncogene Proteins
WNT5A protein, human
Wnt Proteins
Wnt-5a Protein
Wnt11 protein, human
beta Catenin

Grants and funding

This work was supported by the TAMOP-4.2.1.B-10/2/KONV-2010-0002; (Tarsadalmi Megujulas Operativ Program); TIOP 1.3.1-07/1-2F-2008-0002 (Tarsadalmi Infrastruktura Operativ Program); K-OTKA_67807_ A_O7 -2-2012-0093328 (MAG Zrt-NKTH(NFU)-OTKA(Magyar Gazdasagfejlesztesi Kozpont Zrt-Nemzeti Kutatastamogatasi Hivatal (Nemzeti Fejlesztesi Ugynokseg)-Orszagos Tudomanyos Kutatasi Alapprogramok Iroda or Hungarian Scientific Research Fund) all to JEP and by the K-OTKA grant 34039/KA-OTKA/11-02 to DB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.