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.
Highlights
Lung cancer (LC) is the leading cause of cancer death worldwide [1]
About 80% of LCs belongs to the non-small cell lung carcinoma (NSCLC) type which is erroneously considered as a single entity
While Wnts seem to be important in the carcinogenic process of LC-s the complex molecular background of mixed LC types has been notoriously difficult to decipher
Summary
Lung cancer (LC) is the leading cause of cancer death worldwide [1]. About 80% of LCs belongs to the NSCLC type which is erroneously considered as a single entity. The two main NSCLC sub-types, namely AC that arises mostly in the peripheral airways or the bronchio-alveolar region of the parenchyma, and SCC that develops mainly in the proximal airways and affects mostly cigarette smokers, differs in aggressiveness but responsiveness to chemotherapy, . To make the overall picture more complicated, there are an emerging number of combined NSCLCs where malignant tumours are representing themselves as adeno-squamous or mixed type LC. The molecular background of AC and SCC development has been a focus of intense investigation. In various studies Wnt signalling has emerged as one of the potential regulators of the carcinogenic process
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call