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Published on: October 27, 2014
Disruption of the non-canonical WNT pathway in lung squamous cell carcinoma
Eric H L Lee1, Raj Chari, Andy Lam
1Department of Cancer Genetics and Developmental Biology, BC Cancer Agency Research Centre, Vancouver, BC, Canada.
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.
Insights
The non-canonical Wnt pathway is disrupted in over half of lung squamous cell carcinoma samples. This study reveals its significant role in lung cancer, suggesting new therapeutic targets.
Area of Science:
- Molecular Biology
- Oncology
- Gene Expression Analysis
Background:
- Canonical Wnt pathway disruptions are known in cancer.
- The role of the non-canonical Wnt pathway in cancer, particularly lung cancer, is largely unexplored.
Purpose of the Study:
- To investigate Wnt pathway gene expression in lung squamous cell carcinoma.
- To identify disruptions in the non-canonical Wnt pathway in lung cancer.
Main Methods:
- Reverse-transcriptase (RT)-PCR was used to analyze gene expression.
- Examined transcript levels of Wnt pathway genes in tumor and normal lung tissues.
Main Results:
- Over half of lung squamous cell carcinoma samples showed dysregulated non-canonical Wnt pathway gene expression.
- Identified specific gene expression relationships (WNT5A/FZD2, FZD3/DVL2, LRP5/SFRP4) in tumors lacking beta-catenin overexpression.
- Demonstrated non-canonical Wnt pathway gene expression in normal lung tissue and its disruption in cancer.
Conclusions:
- The non-canonical Wnt pathway is frequently disrupted in lung squamous cell carcinoma.
- Findings suggest a more significant role for the non-canonical Wnt pathway in lung cancer than previously understood.
- This pathway represents a potential target for future lung cancer therapies.
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