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Research led by professor of pathology Mikhail Nikiforov, Ph.D., has identified a key mechanism that helps cancer cells spread to the brain, which may lead to a new target for future therapies. The findings were published in the journal Cell Reports in the article "SERINC2-mediated phosphatidylserine remodeling activates protrusion-localized AXL signaling to promote brain metastasis."

Brain metastases are among the most challenging complications of cancer, often leading to poor outcomes and limited treatment options. In the study, researchers investigated how tumor cells gain the ability to migrate, invade surrounding tissue and create new tumors in the brain.

The team identified a protein called SERINC2 as a critical driver of this process. Their research demonstrated that SERINC2 promotes the accumulation of phosphatidylserine, a lipid found in cell membranes, within specialized cellular extensions that cancer cells use for movement and invasion. This accumulation activates AXL, a signaling protein known to regulate cancer cell motility and metastatic behavior.

The study also uncovered another role for SERINC2 in shaping the tumor microenvironment. By promoting the accumulation and release of phosphatidylserine, SERINC2 helps cancer cells communicate with immune cells in the brain, changing their behavior in ways that support tumor growth. The researchers found that lowering SERINC2 levels made cancer cells less invasive and slowed brain tumor growth in animal models.

"These findings provide important new insights into the biological mechanisms that drive brain metastasis," said Nikiforov.

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