Evidence map›Paper›PMID 41741415›Full record

ArticleCell death & disease2026

Deubiquitinase UCH-L1 confers paclitaxel resistance via stabilizing PKM2 to promote glycolysis in triple-negative breast cancer.

Xisha Chen, Xiaoming Zhou, Yingcai Meng, Ying Zhou, Wenjie Zhang, Liyang Yin, Yingying Shen, Jing Zhong, Taolan Zhang, Xuyu Zu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 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

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

1 citing paper in PubMed.

  1. Article
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

10 authors.

Xisha ChenClinical Medical Research Center, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China. chen_xisha@foxmail.com.ORCID http://orcid.org/0000-0003-3091-2919
Xiaoming ZhouNHFY-Biobank, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Yingcai MengDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Ying ZhouClinical Medical Research Center, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Wenjie ZhangClinical Medical Research Center, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Liyang YinClinical Medical Research Center, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Yingying ShenClinical Medical Research Center, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Jing ZhongClinical Medical Research Center, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.ORCID http://orcid.org/0000-0003-4593-4897
Taolan ZhangNHFY-Biobank, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China. TaolZhan@usc.edu.cn.ORCID http://orcid.org/0000-0002-0049-128X
Xuyu ZuClinical Medical Research Center, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China. zuxuyu0108@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Resistance to paclitaxel-based chemotherapy represents a major clinic challenge in triple-negative breast cancer (TNBC). Insights on the regulation genes of chemoresistance and underlying mechanisms in TNBC are waiting for in-depth investigation to address the current treatment bottlenecks. In this study, we identified that ubiquitin carboxyl terminal hydrolase-L1 (UCH-L1) was preferentially overexpressed in TNBC and correlated with worse prognosis as well as poor response to chemotherapy. Upregulation of UCH-L1 attenuated the inhibitory effect of paclitaxel on tumor cells through modulating the aerobic glycolysis, while knockdown of UCH-L1 increased the responsiveness of TNBC cells to the drug both in vitro and in vivo. Coimmunoprecipitation results revealed that the N terminal of UCH-L1 interacts with the C-terminal domain of pyruvate kinase M2 (PKM2). UCH-L1 stabilized PKM2 via removing K48-linked polyubiquitination of PKM2 protein at K498, and thereby promoting glycolysis. Moreover, the expression levels of UCH-L1 and PKM2 were elevated in paclitaxel-resistant TNBC cells, and inhibition of UCH-L1/PKM2 axis-mediated glycolysis markedly sensitized the cells to paclitaxel treatment. Meanwhile, high expression of PKM2 was associated with shorter overall survival in TNBC patients who received chemotherapy. Clinically, PKM2 expression is positively correlated with the expression of UCH-L1 in TNBC tissues. In conclusion, our study reveals that high-expressed UCH-L1 was one of the biomarkers predicting and determining chemosensitivities of TNBC by advancing the cleavage of K48-linked polyubiquitin chains from PKM2 and enhancing glycolysis, and suggests that targeting UCH-L1/PKM2 axis holds great promise for reversing chemoresistance.

Indexed as

Carrier ProteinsDrug Resistance, NeoplasmGlycolysisMembrane ProteinsPaclitaxelThyroid HormonesTriple Negative Breast NeoplasmsUbiquitin ThiolesteraseAnimalsCell Line, TumorFemaleHumansMiceMice, Inbred BALB CMice, NudeThyroid Hormone-Binding ProteinsCarrier ProteinsMembrane ProteinsPaclitaxelThyroid Hormone-Binding ProteinsThyroid HormonesUbiquitin ThiolesteraseUCHL1 protein, human

Identifiers

PMID41741415
PMCPMC12988866

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Registered trials

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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.