Evidence map›Paper›PMID 42226139›Full record

ArticleCellular & molecular biology letters2026

Lactate-activated astrocytes promote NSCLC brain metastasis through extracellular vesicle-mediated miR-8085/TRIM67/ELK1 signaling axis.

Haiqin Peng, Guilong Tanzhu, Wen Shi, Gang Xiao, Qian Zeng, Liu Chen, Xin Wan, Di Jing, Haibin Deng, Thomas Michael Marti and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular & molecular biology letters, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Review
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

12 authors.

Haiqin Peng *Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, China.
Guilong Tanzhu *Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, China.
Wen ShiDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, China.
Gang XiaoDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, China.
Qian ZengDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, China.
Liu ChenDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, China.
Xin WanDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, China.
Di JingDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, China.
Haibin DengDepartment of General Thoracic Surgery, Inselspital, Bern University Hospital, Bern, Switzerland.
Thomas Michael MartiDepartment of General Thoracic Surgery, Inselspital, Bern University Hospital, Bern, Switzerland.
Jun FuClinical Research Center (CRC), Medical Pathology Center (MPC), Cancer Early Detection and Treatment Center (CEDTC) and Translational Medicine Research Center (TMRC), Chongqing University Three Gorges Hospital, Chongqing University, Wanzhou District, Chongqing, 404100, China. jf1977@cqu.edu.cn.
Rongrong ZhouDepartment of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, China. zhourr@csu.edu.cn.

Funding

The Natural Science Foundation of Hunan 2022JJ30992
6 · The paper itself

Abstract

Brain metastasis represents an advanced complication in non-small cell lung cancer (NSCLC), characterized by therapeutic resistance and dismal survival outcomes. Although astrocytes are known to influence tumor progression within the brain microenvironment, their prognostic significance and mechanistic contributions to NSCLC brain metastasis (NSCLC-BM) remain largely unresolved. In this study, we analyze brain metastatic tumors from 66 patients with NSCLC and demonstrate that high infiltration of astrocytes is significantly associated with reduced overall survival. Functional assays reveal that astrocytes enhance the stemness of metastatic tumor cells, a phenotype that is significantly attenuated by silencing astrocytic monocarboxylate transporter 1 (MCT1), thereby blocking lactate uptake. Mechanistically, lactate reprograms astrocytes to release extracellular vesicles enriched in miR-8085, which downregulates the E3 ubiquitin ligase TRIM67 in tumor cells. This suppression stabilizes the transcription factor ELK1 through inhibition of ubiquitin-mediated degradation, promoting stemness maintenance and tumorigenic capacity. Clinically, low TRIM67 and high ELK1 expression correlate with poorer survival in patients with NSCLC-BM. Together, our findings uncover a novel lactate-induced miR-8085/TRIM67/ELK1 signaling cascade that drives brain metastasis progression and highlight potential prognostic biomarkers and therapeutic targets for patients with NSCLC involving the brain.

Indexed as

AstrocytesBrain NeoplasmsCarcinoma, Non-Small-Cell LungExtracellular VesiclesLactic AcidLung NeoplasmsMicroRNAsTripartite Motif ProteinsUbiquitin-Protein LigasesAnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansMonocarboxylate Transport Protein 1Monocarboxylic Acid TransportersSignal TransductionLactic AcidMicroRNAsMonocarboxylate Transport Protein 1Monocarboxylic Acid TransportersTripartite Motif ProteinsUbiquitin-Protein LigasesAstrocyteBrain metastasisExtracellular vesiclesLactateNSCLCTumor stemness

Identifiers

PMID42226139
PMCPMC13523199

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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.