Evidence map›Paper›PMID 39915000›Full record

ArticleJournal for immunotherapy of cancer2025

UBE2T/CDC42/CD276 signaling axis mediates brain metastasis of triple-negative breast cancer via lysosomal autophagy.

Liang Liang Shi, Yan Chen, Ming Xing Xie, Qian Zhi Chen, Xin Wei Qiao, Qi Hong Cheng, Lin Li, Rong Fu, Tao Liang, Xiaobing Jiang and 3 more

Abstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
–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

19 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. NIBAN2/FLII/RREB1 Axis Drives Glioma Stem Cell Malignancy via TLR3 Pathway Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  13. Translational andrology and urology · 2025
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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

13 authors.

Liang Liang Shi *Cancer Center, Wuhan Union Hospital, Wuhan, Hubei, China.
Yan Chen *Department of Ultrasound Medicine, Wuhan Union Hospital, Wuhan, Hubei, China.
Ming Xing XieDepartment of Ultrasound Medicine, Wuhan Union Hospital, Wuhan, Hubei, China.
Qian Zhi ChenDepartment of Breast and Thyroid Surgery, Wuhan Union Hospital, Wuhan, Hubei, China.
Xin Wei QiaoDepartment of Thoracic Surgery, Wuhan Union Hospital, Wuhan, Hubei, China.
Qi Hong ChengDepartment of Neurosurgery, Wuhan Union Hospital, Wuhan, Hubei, China.
Lin LiDepartment of Neurosurgery, Wuhan Union Hospital, Wuhan, Hubei, China.
Rong FuDepartment of Neurosurgery, Wuhan Union Hospital, Wuhan, Hubei, China.ORCID http://orcid.org/0000-0002-7342-263X
Tao LiangDepartment of Clinical Laboratory, Wuhan Union Hospital, Wuhan, Hubei, China.
Xiaobing JiangDepartment of Neurosurgery, Wuhan Union Hospital, Wuhan, Hubei, China.ORCID http://orcid.org/0000-0001-8844-0286
Min Jie Wang *Department of Neurosurgery, Wuhan Union Hospital, Wuhan, Hubei, China.
Jin Yao *Cancer Center, Wuhan Union Hospital, Wuhan, Hubei, China.
Jun Jun Li *Department of Neurosurgery, Wuhan Union Hospital, Wuhan, Hubei, China ljj19891105@126.com.ORCID http://orcid.org/0000-0001-5591-5396

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAdvanced triple-negative breast cancer (TNBC) is prone to brain metastasis (BrM). The precise molecular mechanism responsible for this phenomenon has not yet been completely established, so it is vital to comprehend the molecular mechanism behind it.

methodsThe protein chip analysis was conducted to identify any abnormal UBE2T protein expression in TNBC, especially BrM. Here, we used public databases and bioinformatics analysis as well as clinical samples from different cohorts to investigate the interrelationship between UBE2T/CDC42/CD276. This predicted relationship was then repeatedly validated using different in vivo and in vitro experimental methods. Additionally, multiple experimental approaches were implemented, encompassing western blotting, Co-IP, GST pull-down, flow cytometry, mass spectrometry, immunofluorescence, immunohistochemistry, and qRT-PCR to reveal the molecular mechanism of UBE2T-mediated immune escape and BrM.

resultsOur results indicate that expressed at elevated levels in breast cancer, UBE2T is negatively linked to patient prognosis, especially in BrM of TNBC. Data from clinical samples from our different cohorts and TCGA indicate a significant correlation between UBE2T and immunosuppression. Mechanistically, UBE2T directly interacts with CDC42, promoting its K48-linked polyubiquitination and proteasomal degradation, thereby inhibiting CDC42 from degrading CD276 via the autophagy-lysosomal pathway, indirectly upregulating CD276 and thereby impairing the CD8

conclusionsIn conclusion, our results indicate a new mechanism whereby UBE2T-mediated ubiquitination positively controls the UBE2T/CDC42/CD276 axis to upregulate tumor cell expression of CD276 and thereby impair CD8

Indexed as

AutophagyBrain Neoplasmscdc42 GTP-Binding ProteinLysosomesTriple Negative Breast NeoplasmsUbiquitin-Conjugating EnzymesAnimalsCell Line, TumorFemaleHumansMiceSignal Transductioncdc42 GTP-Binding ProteinCDC42 protein, humanUbiquitin-Conjugating EnzymesBreast CancerCentral Nervous System CancerImmune Checkpoint InhibitorImmunosuppressionImmunotherapy

Identifiers

PMID39915000
PMCPMC11804199

What OpenQuestion holds

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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.