SERINC2 protein emerges as potential target for preventing brain metastasis

A research team led by Mikhail Nikiforov, PhD, Professor of Pathology at Duke University School of Medicine, has identified a molecular mechanism that helps cancer cells migrate, invade surrounding tissue, and establish new tumors in the brain. The work, published on September 22, 2026, in the journal Cell Reports, points to a protein called SERINC2 as a central regulator of this process and suggests it could serve as a target for future therapies aimed at slowing or preventing metastatic disease.

Brain metastases are among the most challenging complications of cancer, often leading to poor outcomes and limited treatment options. In the study, titled “SERINC2-Mediated Phosphatidylserine Remodeling Activates Protrusion-Localized AXL Signaling to Promote Brain Metastasis,” the researchers investigated how tumor cells gain the ability to move, invade, and colonize the brain environment.

The team found that SERINC2 promotes the accumulation of phosphatidylserine, a lipid normally found in cell membranes, within specialized cellular extensions that cancer cells use for movement and invasion. This localized lipid remodeling activates AXL, a signaling protein already known to regulate cancer cell motility and metastatic behavior.

In effect, SERINC2 concentrates a membrane lipid at the leading edge of migrating cells, where it can energize the receptor signaling that drives invasion. The findings go beyond the tumor cell itself. The team uncovered a second role for SERINC2 in shaping the tumor microenvironment: by promoting the accumulation and release of phosphatidylserine, the protein helps cancer cells communicate with immune cells in the brain, changing those cells’ behavior in ways that support tumor growth.

This dual function, one acting on the tumor cell’s own invasive machinery and the other on its surroundings, positions SERINC2 as an influential node in the metastatic cascade. The researchers demonstrated experimentally that lowering SERINC2 levels made cancer cells less invasive and slowed brain tumor growth in animal models, providing direct evidence that the protein’s activity is functionally required for these processes.

“These findings provide important new insights into the biological mechanisms that drive brain metastasis,” said Nikiforov. “By identifying SERINC2 as a key regulator of both cancer cell invasion and interactions with the brain microenvironment, this work highlights a potential new therapeutic target for slowing or preventing metastatic disease.”

The research was conducted as an experimental study with cells as the primary subject of investigation, complemented by animal models of brain metastasis. As with all preclinical work, the results establish a mechanism and a candidate target rather than a validated treatment; translating the findings into therapies for patients will require further investigation, including the development of agents capable of modulating SERINC2 or the pathways it controls.

The authors and the institution frame the work as a foundation for future studies into therapies that target SERINC2 and related signaling pathways, rather than as an immediate clinical advance. By concentrating phosphatidylserine in the protrusions that cancer cells extend as they move, SERINC2 appears to couple the cell’s lipid geography to its signaling state, ensuring that AXL activation occurs where motility is initiated. The same lipid redistribution, when released from the cell surface, reaches immune cells in the brain and alters their behavior in a manner favorable to tumor expansion.

Duke School of Medicine describes the work as part of its commitment to translational research that can inform the development of future therapies for patients with advanced cancer while deepening scientific understanding of how cancers spread and interact with their surrounding environment. As researchers continue to seek more effective treatments for metastatic disease, the study provides a basis for future investigations into therapies that target SERINC2 and the signaling pathways it regulates.

Subject of Research: SERINC2-mediated phosphatidylserine remodeling and AXL signaling in brain metastasis

Article Title: Duke pathology research identifies potential new target for preventing brain metastasis

Article References: Duke pathology research identifies potential new target for preventing brain metastasis. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: brain metastasis, SERINC2, phosphatidylserine, AXL signaling, cancer cell invasion, tumor microenvironment, Cell Reports, Duke University, experimental study, metastatic cancer, lipid remodeling, therapeutic target