CRISPR activation screen in mice identifies novel membrane proteins enhancing pulmonary metastatic colonisation.
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Date
2021-03-23Author
van der Weyden, L
Harle, V
Turner, G
Offord, V
Iyer, V
Droop, A
Swiatkowska, A
Rabbie, R
Campbell, AD
Sansom, OJ
Pardo, M
Choudhary, JS
Ferreira, I
Tullett, M
Arends, MJ
Speak, AO
Adams, DJ
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Research team
Functional Proteomics Group
Functional Proteomics Group
Language
eng
Date accepted
2021-02-25
License start date
2021-03-23
Citation
Communications biology, 2021, 4 (1), pp. 395 - ?
Publisher
NATURE PORTFOLIO