Disruption of the Non-Canonical WNT Pathway in Lung Squamous Cell Carcinoma

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.