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

• Published in: PloS one 2013-03, Vol.8 (3), p.e57393
• Main Authors: Bartis, Domokos, Csongei, Veronika, Weich, Alexander, Kiss, Edit, Barko, Szilvia, Kovacs, Tamas, Avdicevic, Monika, D'Souza, Vijay K, Rapp, Judit, Kvell, Krisztian, Jakab, Laszlo, Nyitrai, Miklos, Molnar, Tamas F, Thickett, David R, Laszlo, Terezia, Pongracz, Judit E
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Analysis; beta Catenin - metabolism; Biology; Biotechnology; Cadherin; Cadherins; Cancer; Cancer research; Carcinogens; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Cell Line, Tumor; Cell Transformation, Neoplastic - metabolism; Cigarette smoke; Epithelial cells; Gene expression; Gene Expression Regulation, Neoplastic; Health aspects; Health risks; Humans; Immunology; Kinases; Lung cancer; Lung carcinoma; Lung diseases; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Medical schools; Medicine; Melanoma; Metastasis; Motility; Non-small cell lung cancer; Non-small cell lung carcinoma; Nuclei; Nuclei (cytology); Protein Transport; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Regulations; Relocation; Respiratory tract; Signal transduction; Signaling; Skin cancer; Small cell lung carcinoma; Smoke; Smoking; Squamous cell carcinoma; Surgery; Target recognition; Tumor cell lines; Tumors; Up-regulation; Wnt protein; Wnt Proteins - genetics; Wnt Proteins - metabolism; Wnt Signaling Pathway; Wnt-5a Protein; β-Catenin
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0057393

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.