부산대학교 도서관

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. Louise van der Weyden et al. report a CRISPRa screen in mice to identify membrane protein-encoding genes that, when overexpressed, enhance the metastatic potential of melanoma cells. They find that high expression of LRRN4CL in melanoma cells increases lung metastases in mice and correlates with poorer survival in melanoma patients, suggesting it could be a promising drug target. [ABSTRACT FROM AUTHOR]