Evidence map›Paper›PMID 42721038›Full record

ArticleCell reports2026

SERINC2-mediated phosphatidylserine remodeling activates protrusion-localized AXL signaling to promote brain metastasis.

Zhibo Yan, Maja Beus, Zhannan Han, Lihong Pan, Yihui Wang, Junqi Lu, Loren B Weidenhammer, Liang Liu, Spencer Rosario, Jingyun Lee and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Zhibo YanDepartment 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.
Maja BeusDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA.
Zhannan HanDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA.
Lihong PanDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA.
Yihui WangDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA.
Junqi LuDepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA.
Loren B WeidenhammerDepartment of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.
Liang LiuDepartment of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA.
Spencer RosarioDepartment of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Jingyun LeeDepartment of Internal Medicine, Section of Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA.
Cristina M FurduiDepartment of Internal Medicine, Section of Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA.
Hui-Wen LoDepartment of Cell Biology and Genetics, Naresh K. Vashisht College of Medicine, Texas A&M University, College Station, TX, USA.
Eugene S KandelDepartment of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Erik J SoderblomProteomics and Metabolomics Core Facility, Duke University School of Medicine, Durham, NC, USA, Durham, NC 27710, USA.
Weili MaCancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Qing ChenCancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Sergei V KotenkoDepartment of Microbiology, Biochemistry and Molecular Genetics, Center for Cell Signaling, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.
Raymond B BirgeDepartment of Microbiology, Biochemistry and Molecular Genetics, Center for Cell Signaling, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.
Mikhail A NikiforovDepartment 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. Electronic address: mikhail.nikiforov@duke.edu.

Funding

Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI DONNA NIEDZWIECKI · 1985 to 2026
$174.8M
The role of regulation and subcellular localization of GTP biosynthesis in melanoma invasion and metastasisR01CA279129 · NCI · DUKE UNIVERSITY · PI Mikhail Nikiforov · 2023 to 2026
$2.0M
NCI NIH HHS P30 CA014236NCI NIH HHS R01 CA279129
6 · The paper itself

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.

Indexed as

Brain NeoplasmsCell Surface ExtensionsMembrane ProteinsPhosphatidylserinesPhospholipid Transfer ProteinsProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesAnimalsAxl Receptor Tyrosine KinaseCell Line, TumorHumansMiceSignal TransductionTumor MicroenvironmentAXL protein, humanAxl Receptor Tyrosine KinaseMembrane ProteinsPhosphatidylserinesPhospholipid Transfer ProteinsProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesAXLbrain metastasesbreast cancercell protrusionsCP: cancerCP: cell biologyinvasionmelanomaOSBPL8phosphatidylserineSERINC2

Identifiers

PMID42721038
PMCPMC13671829

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.