CRISPR activation screen in mice identifies novel membrane proteins enhancing pulmonary metastatic colonisation

van der Weyden, L. et al. (2021) CRISPR activation screen in mice identifies novel membrane proteins enhancing pulmonary metastatic colonisation. Communications Biology, 4, 395. (doi: 10.1038/s42003-021-01912-w) (PMID:33758365) (PMCID:PMC7987976)

Abstract

Melanoma represents ~5% of all cutaneous malignancies, yet accounts for the majority of skin cancer deaths due to its propensity to metastasise. To develop new therapies, novel target molecules must to be identified and the accessibility of cell surface proteins makes them attractive targets. Using CRISPR activation technology, we screened a library of guide RNAs targeting membrane protein-encoding genes to identify cell surface molecules whose upregulation enhances the metastatic pulmonary colonisation capabilities of tumour cells in vivo. We show that upregulated expression of the cell surface protein LRRN4CL led to increased pulmonary metastases in mice. Critically, LRRN4CL expression was elevated in melanoma patient samples, with high expression levels correlating with decreased survival. Collectively, our findings uncover an unappreciated role for LRRN4CL in the outcome of melanoma patients and identifies a potential therapeutic target and biomarker.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sansom, Professor Owen and Campbell, Dr Andrew
• Authors: van der Weyden, L., Harle, V., Turner, G., Offord, V., Iyer, V., Droop, A., Swiatkowska, A., Rabbie, R., Campbell, A. D., Sansom, O. J., Pardo, M., Choudhary, J. S., Ferreira, I., Tullett, M., Arends, M. J., Speak, A. O., and Adams, D. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Communications Biology
• Publisher: Nature Research
• ISSN: 2399-3642
• ISSN (Online): 2399-3642
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Communications Biology 4: 395
• Publisher Policy: Reproduced under a Creative Commons License