CRISPR activation screen in mice identifies novel membrane proteins enhancing pulmonary metastatic colonisation.
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ICR Authors
Authors
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
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
Document Type
Journal Article
Date
2021-03-23
Date Accepted
2021-02-25
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.
Citation
Communications biology, 2021, 4 (1), pp. 395 - ?
Source Title
Publisher
NATURE PORTFOLIO
ISSN
2399-3642
eISSN
2399-3642
Collections
Research Team
Functional Proteomics Group
Functional Proteomics Group
Functional Proteomics Group