Related Experiment Video
Updated: Sep 12, 2026

Modeling Brain Metastasis Via Tail-Vein Injection of Inflammatory Breast Cancer Cells
Published on: February 4, 2021
SERINC2-mediated phosphatidylserine remodeling activates protrusion-localized AXL signaling to promote brain
Zhibo Yan1, Maja Beus2, Zhannan Han2
1Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA.
Abstract:
Cell protrusions (CPs) promote metastasis by coordinating cell invasion, matrix remodeling, and communication with the microenvironment. The receptor tyrosine kinase AXL, activated in brain-tropic metastatic cancers, frequently localizes to CPs. The metabolic cues regulating CP biogenesis and AXL activation remain unclear. Here, we report that in invading cancer cells, phosphatidylserine is the most enriched lipid class in CPs. Mechanistically, we demonstrate that the scramblase-like transmembrane protein SERINC2 functions as a scaffold that interacts with integrins and recruits OSBPL8, an ER-plasma-membrane phosphatidylserine transporter, to CPs. This recruitment leads to phosphatidylserine accumulation and externalization at CPs, activation of CP-localized AXL, and upregulation of cell invasion. Furthermore, extracellular vesicles enriched in phosphatidylserine in a SERINC2-dependent manner stimulate autocrine AXL activation and drive M2-like microglia polarization. Accordingly, SERINC2 enhances orthotopic brain tumor growth and microglial reprogramming in vivo. Our data reveal a SERINC2-OSBPL8 axis orchestrating spatial lipid remodeling, AXL activation, and tumor-microenvironment communication.
More Related Videos
Related Concept Videos
Cancer Cell Migration through Invadopodia
Intracellular Signaling Affects Focal Adhesions
Some...
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
PI3K/mTOR/AKT Signaling Pathway
The JAK-STAT Signaling Pathway
Abnormal Proliferation
