Evidence map›Paper›PMID 42333921›Full record

ArticleAging cell2026

Oxidative Stress Induced Senescent Macrophage-Driven Squamous Cell Carcinoma Invasion via Glutamine Metabolic Reprogramming.

Shimeng Wang, Jingtian Mu, Wei Zhao, Can Hu, Xueke Shi, Hongmei Zhou, Junjiang Liu, Fanglong Wu

Abstract read
In one paragraph

Article in Aging cell, 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

8 authors.

Shimeng WangState Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Jingtian MuState Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Wei ZhaoState Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Can HuState Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Xueke ShiState Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Hongmei ZhouState Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.ORCID https://orcid.org/0000-0003-2985-3536
Junjiang LiuState Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Fanglong WuState Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.

Funding

National Key Research and Development Program of China 2023YFC3605600National Natural Science Foundation of China 82301094National Natural Science Foundation of China 82301095National Natural Science Foundation of China 82370963National Natural Science Foundation of China 82573832Sichuan Province Science and Technology Support Program 2026NSFSC0673
6 · The paper itself

Abstract

Oxidative stress drives tumor microenvironment (TME) remodeling by inducing metabolic reprogramming and cellular senescence. Glutamine, a key substrate supporting oxidative stress defense, has been implicated in TME remodeling and metastasis, yet its specific role in initiating tumor invasion remains unclear. Here, oxidative stress induced the generation of senescent macrophages in the TME, and clinical samples showed that their accumulation positively correlates with malignancy. We established cisplatin- and radiation-induced senescent macrophage models that exhibited distinct senescence-associated secretory phenotypes (SASP) and enhanced squamous cell carcinoma (SCC) migration and invasion. Integrated metabolomic and transcriptomic analyses revealed the glutamine-glutamate pathway as a central metabolic hub, with glutaminase 2 upregulated to drive glutaminolysis and strongly associated with IL-1β expression. Mechanistically, IL-1β secreted by senescent macrophages promoted tumor invasion by downregulating IL-1R2 and activating NF-κB signaling in SCC cells. Targeting the glutamine metabolism-regulated IL-1β/IL-1R2 axis effectively suppressed SCC invasion. These findings uncover a novel metabolic mechanism linking glutamine metabolism to SASP regulation and suggest a therapeutic strategy to limit SCC invasion.

Indexed as

Carcinoma, Squamous CellCellular SenescenceGlutamineMacrophagesOxidative StressAnimalsCell Line, TumorHumansInterleukin-1betaMetabolic ReprogrammingMiceNeoplasm InvasivenessTumor MicroenvironmentGlutamineInterleukin-1betaglutamine metabolism reprogrammingoxidative stresssenescence‐associated secretory phenotypesenescent macrophagessquamous cell carcinoma

Identifiers

PMID42333921
PMCPMC13288175

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.