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Publications of the Week

Epithelial Tumour Suppressor ELF3 Is a Lineage-Specific Amplified Oncogene in Lung Adenocarcinoma

By December 11, 2019December 16th, 2019No Comments

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This week we profile a recent publication in Nature Communications involving
Erin Marshall (pictured) in the laboratory of Dr. Wan Lam at BC Cancer.

Can you provide a brief overview of your lab’s current research focus?

The Lam Lab currently focuses on genetic and genomic methods of discovering new cancer drivers, in particular in lung cancer. Wan’s team develops novel whole genome technologies and bioinformatics methodologies for tracking genetic, epigenetic, and gene expression changes in order to identify genes that govern cancer progression and treatment responses. The major pillars of discovery that the lab is focuses on include understanding the lung tumour microenvironment in cancer initation and progression, understanding environmental factors that lead to lung cancer, and assessing the contribution of other comorbidities to lung cancer development, including COPD.

What is the significance of the findings in this publication?

We find that ELF3, a transcription factor, is a new amplified oncogene in approximately 80% of all lung adenocarcinomas (LUAD), the largest subtype of lung cancer. Using a mouse model, we find that LUAD cells that express ELF3 are selected for in implanted tumours, and ELF3 expression is required for tumour growth. We also see that in human LUAD tumours, high expression of ELF3 is associated with poor patient outcome, indicating the importance of ELF3 to LUAD biology. This study is important because it provides substantial evidence that ELF3 does not just act as a tumour suppressor, as has been described in a variety of cancer types already. It highlights the importance of lineage-specific cellular biology, particularly in the context of cancer research. We know that lineage is an important determinant of specific biological functions within a cell, and this work brings to light the importance of considering the impact of cellular context on gene deregulation in cancer.

What are the next steps for this research?

In this project, we found that preventing ELF3 expression inhibited LUAD tumour growth in a mouse model. These promising results indicate the inhibiting ELF3 could be a new therapy for human tumours, and we are working to establish the best way to inhibit this target.

If you’d like us to mention your funding sources, please list them.

This work was supported by the Canadian Institutes for Health Research.

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