Targetable Gene Identified that Plays Key Role in Metastasis of Cancer to the Lungs

Targetable Gene Identified that Plays Key Role in Metastasis of Cancer to the Lungs

Researchers at the Wellcome Sanger Institute have identified a gene that plays a role in the metastasis of cancer to the lungs. The LRRN4CL gene, which had not previously been linked to cancer, was found to increase the likelihood of melanoma metastasizing to the lungs in mice when it was over expressed.

Further studies revealed over expression of the LRRN4CL gene also increased the likelihood of other cancers metastasizing to the lungs, including breast, colon, and bladder cancers.

Metastasis is when cancers become mobile in the body and spread from the primary organ to other organs in the body through the blood and lymphatic system. Once cancers have metastasized and secondary tumors have formed in other organs, they are far more difficult to treat and the prognosis for patients is poor. The lungs are a common site for secondary tumors to form.

One of the reasons melanoma is so deadly is because it is common for the cancer to metastasize. Identifying a gene that plays a role in metastasis that could be targeted with drug therapy could greatly improve survival rates. Fortunately, the LRRN4CL gene would serve as a good target for drug therapy. The LRRN4CL gene encodes a protein which is found on the surface of cancer cells, but the gene is expressed at low levels in the rest of the body. Developing a drug that targets the LRRN4CL gene would therefore be unlikely to cause major side effects.

To identify genes that potentially played a role in the metastasis of melanoma to the lungs, the researchers conducted a CRISPR activation screen on genes that encoded proteins on the surface of cells. They increased expression of those genes and determined the effect they had on metastasis. After identifying the LRRN4CL gene’s possible role in metastasis, the researchers checked gene expression databases for tumors in humans and found that individuals with melanomas that had high expression of LRRN4CL had poorer outcomes.

“Prior to this study, there was nothing in the scientific literature to link the LRRN4CL gene to cancer, much less to suggest that it plays such a pivotal role in metastasis,” said Dr David Adams, senior author of the paper. “Part of the power of CRISPR screens is that they don’t require a clear hypothesis to create new insights. This is an important discovery that marks LRRN4CL as a promising drug target to help prevent the spread of cancer to the lungs and improve outcomes for patients.”

You can read more about the study in the paper – CRISPR activation screen in mice identifies novel membrane proteins enhancing pulmonary metastatic colonisation – which was recently published in the journal Communications Biology. DOI: 10.1038/s42003-021-01912-w