Eric H.L. Lee^1,6, Raj Chari^1,6, Andy Lam¹, Raymond T. Ng^1,2, John Yee³, John English⁴, Kenneth G. Evans³, Calum MacAulay⁵, Stephen Lam⁵ and Wan L. Lam¹

¹Department of Cancer Genetics and Developmental Biology, BC Cancer Agency Research Centre, Vancouver, BC, Canada. ²Department of Computer Science, University of British Columbia, Vancouver, BC, Canada. ³Department of Surgery, Vancouver General Hospital, Vancouver, BC, Canada. ⁴Department of Pathology, Vancouver General Hospital, Vancouver, BC, Canada. ⁵Department of Cancer Imaging, BC Cancer Agency Research Centre, Vancouver, BC, Canada. ⁶These authors contributed equally.

Abstract

Disruptions of beta-catenin and the canonical Wnt pathway are well documented in cancer. However, little is known of the non-canonical branch of the Wnt pathway. In this study, we investigate the transcript level patterns of genes in the Wnt pathway in squamous cell lung cancer using reverse-transcriptase (RT)-PCR. It was found that over half of the samples examined exhibited dysregulated gene expression of multiple components of the non-canonical branch of the WNT pathway. In the cases where beta catenin (CTNNB1) was not over-expressed, we identified strong relationships of expression between wingless-type MMTV integration site family member 5A (WNT5A)/frizzled homolog 2 (FZD2), frizzled homolog 3 (FZD3)/dishevelled 2 (DVL2), and low density lipoprotein receptor-related protein 5 (LRP5)/secreted frizzled-related protein 4 (SFRP4). This is one of the first studies to demonstrate expression of genes in the non-canonical pathway in normal lung tissue and its disruption in lung squamous cell carcinoma. These findings suggest that the non-canonical pathway may have a more prominent role in lung cancer than previously reported.