Evidence map›Paper›PMID 41832564›Full record

ArticleJournal of translational medicine2026

M2-like GAMs secreting CSTA drive glioblastoma progression via the ITGB4-TGFB1 feedback axis.

Jiasheng Wu, Haohao Huang, Xinbo Li, Hongtao Zhu, Yixuan Ma, Xiaojin Liu, Hongbin Liu, Suojun Zhang, Huaqiu Zhang, Ting Lei and 3 more

Abstract read
In one paragraph

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

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

13 authors.

Jiasheng Wu *Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Haohao Huang *Department of Neurosurgery, General Hospital of Central Theatre Command of People's Liberation Army, Wuhan, China.
Xinbo LiDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hongtao ZhuDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yixuan MaDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Xiaojin LiuDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hongbin LiuDepartment of Neurosurgery, General Hospital of Central Theatre Command of People's Liberation Army, Wuhan, China.
Suojun ZhangDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Huaqiu ZhangDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ting LeiDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ran LiDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. liran@tjh.tjmu.edu.cn.
Kai ShuDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. kshu@tjh.tjmu.edu.cn.
Chao YouDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. youchao@tjh.tjmu.edu.cn.ORCID 0009-0006-0327-0788

Funding

China Postdoctoral Science Foundation 2021MD703960China Postdoctoral Science Foundation 2022MD711253General Hospital of People's Liberation Army ZZYCZ202107General Hospital of People's Liberation Army ZZYKF202202Key Technologies Research and Development Program 2022YFC2403905Key Technologies Research and Development Program 2023YFC2510000National Natural Science Foundation of China 82072805National Natural Science Foundation of China 82203879National Natural Science Foundation of China 82403476Natural Science Foundation of Hubei Province 2022CFB883Natural Science Foundation of Hubei Province 2023AFB135Natural Science Foundation of Hubei Province 2023AFB712Wuhan Science and Technology Project 2021022002023426Wuhan Science and Technology Project 2024040801020362
6 · The paper itself

Abstract

backgroundTumor microenvironment (TME) remodeling is a hallmark of gliomas. Glioma-associated macrophage/microglia (GAMs), the most abundant cellular component in the glioma TME, play critical roles in driving glioma progression, though the specific GAM subsets and their regulatory mechanisms remain unclear. This study investigates glioma-GAM crosstalk, identifies GAM subsets that regulate glioblastoma (GBM) progression, clarifies the role and mechanism of CSTA, and explores its clinical relevance.

methodsWith bulk RNA-seq and scRNA-seq datasets, a CSTA⁺ M2-like GAM subset was identified. In vitro and in vivo models confirmed CSTA’s pro-oncogenic effect on GBM. In vitro studies explored the mechanisms of CSTA upregulation in M2-like GAMs and its role in advancing GBM progression. Mass spectrometry and molecular docking predicted and validated CSTA’s interacting protein targets. Clinical cohort analyses evaluated the relationship between CSTA and glioma grades.

resultsM2-like polarization activates p44/p42 (ERK1/2) phosphorylation in the MAPK pathway, upregulating the c-JUN/c-FOS (AP-1) transcription complex and promoting CSTA expression in GAMs. CSTA binds to ITGB4 at glutamate residue 88, activating downstream NF-κB and MAPK signaling in GBM cells to drive progression. Moreover, the CSTA-ITGB4 axis induces GBM cells to secrete TGFB1, which recruits M2-like GAMs and exacerbates TME immunosuppression. Additionally, CSTA levels in peripheral blood and cerebrospinal fluid (CSF) correlate positively with glioma grade.

conclusionsCSTA⁺ M2-like GAMs promote GBM malignancy via the CSTA-ITGB4 axis, activating downstream NF-κB and MAPK signaling and forming a TGFB1-mediated positive feedback loop. Notably, CSTA correlates with glioma grades and has independent prognostic and potential therapeutic value.

Indexed as

Brain NeoplasmsDisease ProgressionFeedback, PhysiologicalGlioblastomaMacrophagesMicrogliaTransforming Growth Factor beta1AnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansMolecular Docking SimulationSignal TransductionTumor MicroenvironmentTransforming Growth Factor beta1CSTAGlioblastomaGlioma associated macrophages/microgliaIntegrin β4Molecular docking

Identifiers

PMID41832564
PMCPMC13101109

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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.