Evidence map›Paper›PMID 41618295›Full record

ArticleRespiratory research2026

GJB2 drives LUAD progression in part via cAMP-mediated M2 macrophage polarization through the PKA-CREB pathway.

Yuanhua Liu, Guanghui Liu, Jingjing Mei, Jia Li, Jiming Si, Yan Kang, Jianjun Jin

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Respiratory research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Beyond the gap: moonlighting functions of connexins in cancer.Cell communication and signaling : CCS · 2026
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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Yuanhua Liu *Department of respiratory medicine, The first affiliated hospital of zhengzhou university, Zhengzhou, Henan, 450008, PR China.
Guanghui Liu *Department of gastrointestinal surgery, The first affiliated hospital of zhengzhou university, Zhengzhou, Henan, 450008, PR China.
Jingjing MeiDepartment of respiratory medicine, The first affiliated hospital of zhengzhou university, Zhengzhou, Henan, 450008, PR China.
Jia LiDepartment of respiratory medicine, The first affiliated hospital of zhengzhou university, Zhengzhou, Henan, 450008, PR China.
Jiming SiDepartment of respiratory medicine, The first affiliated hospital of zhengzhou university, Zhengzhou, Henan, 450008, PR China.
Yan KangDepartment of respiratory medicine, The first affiliated hospital of zhengzhou university, Zhengzhou, Henan, 450008, PR China.
Jianjun JinDepartment of respiratory medicine, The first affiliated hospital of zhengzhou university, Zhengzhou, Henan, 450008, PR China. JianjunJin2017@163.com.

Funding

Key scientific Research Project Plan of Colleges and universities of Henan Province 23A320014
6 · The paper itself

Abstract

backgroundM2 macrophage polarization is a key driver of lung adenocarcinoma (LUAD) progression, yet its underlying regulatory mechanisms remain unclear. The expression pattern and biological function of the gap junction protein GJB2 in LUAD have not been elucidated to date.

methodsTCGA database analysis was used to determine GJB2 expression in LUAD and its correlation with prognosis. GJB2 knockdown (KD) and overexpression (OE) models were established in A549/NCI-H1975 cells. EdU, Transwell, and flow cytometry assays evaluated LUAD cell proliferation, migration, invasion, and apoptosis. A LUAD-THP-1 macrophage co-culture system, cAMP agonist/inhibitor treatment, and PKA-CREB pathway analysis were applied to explore mechanisms. Nude mouse xenograft models validated findings in vivo.

resultsGJB2 was significantly upregulated in LUAD tissues and correlated with reduced overall survival. GJB2-KD inhibited LUAD cell malignant behaviors and promoted apoptosis, while GJB2-OE exerted opposite effects. GJB2 mediated gap junction-dependent cAMP transfer to macrophages, activating the PKA-CREB axis to induce M2 polarization; cAMP agonists reversed GJB2-KD effects. In vivo, GJB2-KD suppressed tumor growth, reduced serum cAMP and M2 cytokines, and inhibited PKA/CREB phosphorylation.

conclusionsThe GJB2-cAMP-PKA-CREB axis drives LUAD progression by inducing M2 macrophage polarization. GJB2 may serve as a novel prognostic biomarker and potential therapeutic target for LUAD.

Indexed as

Adenocarcinoma of LungConnexin 26Cyclic AMPCyclic AMP-Dependent Protein KinasesCyclic AMP Response Element-Binding ProteinDisease ProgressionLung NeoplasmsMacrophagesAnimalsCell Line, TumorCell PolarityHumansMaleMiceMice, NudeSignal TransductionConnexin 26CREB1 protein, humanCyclic AMPCyclic AMP-Dependent Protein KinasesCyclic AMP Response Element-Binding ProteinGJB2 protein, humancAMPGJB2LUADMacrophage polarizationPKA-CREB signaling pathway

Identifiers

PMID41618295
PMCPMC12934008

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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.