Related Experiment Video

Updated: Jan 13, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

623

JAM3 orchestrates Mac-1-dependent AKT phosphorylation to facilitate neutrophil extracellular trap-driven meningioma

Jing Zhang1, Yipeng Dong1, Xianghua Zhang1

  • 1Department of Neurosurgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.

Cellular Signalling
|January 7, 2026
PubMed

Insights

JAM3 protein promotes meningioma growth by triggering neutrophil extracellular traps (NETs) via the Mac-1/AKT pathway. Inhibiting this interaction may offer new treatments for these brain tumors.

Area of Science:

  • Neuro-oncology
  • Immunology
  • Cell Biology

Background:

  • Neutrophil extracellular traps (NETs) are implicated in various cancers.
  • The role of NETs in meningioma pathogenesis is not well understood.

Purpose of the Study:

  • To elucidate the mechanism by which JAM3 promotes meningioma development through NETs.
  • To investigate the JAM3/Mac-1 interaction and its effect on the AKT pathway and neutrophil function.

Main Methods:

  • Co-immunoprecipitation (Co-IP) to confirm protein interactions.
  • In vitro co-culture assays with meningioma cells and neutrophils.
  • In vivo xenograft mouse models.
  • Pharmacological manipulation using AKT activator SC79 and DNase I.

Main Results:

  • JAM3 knockdown reduced AKT phosphorylation, neutrophil migration, and NET formation, which was rescued by SC79.
  • JAM3/Mac-1 interaction was confirmed by Co-IP.
  • JAM3 knockdown inhibited tumor growth and intratumoral NETs in vivo.
  • NETs promoted meningioma cell growth, an effect blocked by DNase I.
  • Mac-1 knockdown in neutrophils impaired function, restored by SC79.
  • Clinical meningioma samples showed correlation between JAM3, Mac-1, and NET markers.

Conclusions:

  • JAM3 promotes meningioma development by regulating NET formation via the Mac-1/AKT axis.
  • Targeting the JAM3/Mac-1/AKT pathway could be a therapeutic strategy for meningiomas.
Keywords:
AKTJAM3Mac-1MeningiomaNeutrophilNeutrophil extracellular traps (NETs)

More Related Videos

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

6.4K
A Macrophage Reporter Cell Assay to Examine Toll-Like Receptor-Mediated NF-kB/AP-1 Signaling on Adsorbed Protein Layers on Polymeric Surfaces07:55

A Macrophage Reporter Cell Assay to Examine Toll-Like Receptor-Mediated NF-kB/AP-1 Signaling on Adsorbed Protein Layers on Polymeric Surfaces

Published on: January 7, 2020

7.8K

Related Concept Videos

cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
8.3K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.9K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
3.5K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.3K
Microtubule Associated Proteins (MAPs)01:42

Microtubule Associated Proteins (MAPs)

Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
5.8K
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
14.2K