Evidence map›Paper›PMID 41306556›Full record

ArticleMedComm2025

mTORC1-USP30-LEF1 Cascade Regulates Cancer Stemness and Malignant Progression Through Mitonuclear Crosstalk.

Xiaolin Li, Haowei Zhang, Jia Li, Cheng Luo, Zijian Yang, Jin Cai, Li Xia, Yapei Jiang, Ruonan Wang, Hongli Zeng and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in MedComm, 2025. 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. Article
  2. 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

16 authors.

Xiaolin LiSchool of Food and Drug Shenzhen Polytechnic University Shenzhen China.
Haowei ZhangState Key Laboratory of Chemical Oncogenomics Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate School Tsinghua University Shenzhen China.
Jia LiState Key Laboratory of Chemical Oncogenomics Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate School Tsinghua University Shenzhen China.
Cheng LuoState Key Laboratory of Chemical Oncogenomics Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate School Tsinghua University Shenzhen China.
Zijian YangDepartment of Breast and Thyroid Surgery Peking University Shenzhen Hospital Shenzhen China.
Jin CaiState Key Laboratory of Chemical Oncogenomics Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate School Tsinghua University Shenzhen China.
Li XiaState Key Laboratory of Chemical Oncogenomics Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate School Tsinghua University Shenzhen China.
Yapei JiangState Key Laboratory of Chemical Oncogenomics Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate School Tsinghua University Shenzhen China.
Ruonan WangState Key Laboratory of Chemical Oncogenomics Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate School Tsinghua University Shenzhen China.
Hongli ZengState Key Laboratory of Chemical Oncogenomics Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate School Tsinghua University Shenzhen China.
Yuetong LiState Key Laboratory of Chemical Oncogenomics Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate School Tsinghua University Shenzhen China.
Haitao YangState Key Laboratory of Chemical Oncogenomics Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate School Tsinghua University Shenzhen China.
Tong GaoState Key Laboratory of Chemical Oncogenomics Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate School Tsinghua University Shenzhen China.
Weidong XieState Key Laboratory of Chemical Oncogenomics Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate School Tsinghua University Shenzhen China.
Yaou ZhangState Key Laboratory of Chemical Oncogenomics Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate School Tsinghua University Shenzhen China.
Naihan XuSchool of Food and Drug Shenzhen Polytechnic University Shenzhen China.ORCID https://orcid.org/0000-0001-5457-6863

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

USP30, a ubiquitin-specific protease, primarily characterized as a mitochondrial deubiquitinase regulating mitophagy, has not been previously reported to have nuclear functions. In this study, we demonstrate that USP30 is present in both mitochondrial and nuclear compartments. Nutrient deprivation triggers USP30 nuclear translocation via an N-terminal nuclear localization signal (NLS), mediated through suppression of mTORC1-dependent phosphorylation at serine 104, a modification constraining nuclear entry. Nuclear USP30 acts as a tumor suppressor by inhibiting cancer stemness and chemoresistance in triple-negative breast cancer (TNBC) cells. Mechanistically, USP30 directly interacts with and deubiquitinates the transcription factor TCF/LEF1 at K379 and K382 residues, disrupting recruitment of CBP/P300 co-activators to the β-catenin/LEF1 complex. This abolishes β-catenin/LEF1 transactivation and suppresses WNT signaling. Clinically, USP30 is downregulated in TNBC and cancer stem cells (CSCs), with notably reduced nuclear levels in cancer tissues. Overexpression of nuclear USP30 markedly reduces lung metastatic burden in TNBC mouse models. These findings uncover a novel role for nuclear USP30 in regulating cancer stemness and suggest that targeting the dynamic relocalization of USP30 from mitochondria to the nucleus could offer new therapeutic strategies for breast cancer metastasis.

Indexed as

chemoresistancedeubiquitinationstemnessTCF/LEF1USP30WNT

Identifiers

PMID41306556
PMCPMC12644247

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.