title: Down-regulation of canonical and up-regulation of non-canonical Wnt signalling in the carcinogenic process of squamous cell lung carcinoma.
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.
authors.affiliation: Department of Medical Biotechnology, Institute of Immunology and Biotechnology, Medical School, University of Pecs, Pecs, Hungary.
authors.forename: Domokos
authors.initials: D
authors.lastname: Bartis
authors.forename: Veronika
authors.initials: V
authors.lastname: Csongei
authors.forename: Alexander
authors.initials: A
authors.lastname: Weich
authors.forename: Edit
authors.initials: E
authors.lastname: Kiss
authors.forename: Szilvia
authors.initials: S
authors.lastname: Barko
authors.forename: Tamas
authors.initials: T
authors.lastname: Kovacs
authors.forename: Monika
authors.initials: M
authors.lastname: Avdicevic
authors.forename: Vijay K
authors.initials: VK
authors.lastname: D'Souza
authors.forename: Judit
authors.initials: J
authors.lastname: Rapp
authors.forename: Krisztian
authors.initials: K
authors.lastname: Kvell
authors.forename: Laszlo
authors.initials: L
authors.lastname: Jakab
authors.forename: Miklos
authors.initials: M
authors.lastname: Nyitrai
authors.forename: Tamas F
authors.initials: TF
authors.lastname: Molnar
authors.forename: David R
authors.initials: DR
authors.lastname: Thickett
authors.forename: Terezia
authors.initials: T
authors.lastname: Laszlo
authors.forename: Judit E
authors.initials: JE
authors.lastname: Pongracz
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D000071818:Wnt-5a Protein; D051176:beta Catenin / Q000378:metabolism
chemical_list: D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C540523:Wnt11 protein, human; D051176:beta Catenin