Evidence map›Paper›PMID 36725886›Full record

ArticleOncogene2023

Deubiquitylation of Rab35 by USP32 promotes the transmission of imatinib resistance by enhancing exosome secretion in gastrointestinal stromal tumours.

Chao Li, Zhishuang Gao, Zhiwei Cui, Zonghang Liu, Yibo Bian, Haoyu Sun, Nuofan Wang, Zhongyuan He, Bowen Li, Fengyuan Li and 6 more

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
7.3field-weighted citation impact, top 2% of its field
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

17 citing papers in PubMed, 23 citations in OpenAlex.

  1. Deubiquitination of Vangl by USP6 and USP32 Regulates Planar Cell Polarity Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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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

16 authors at 2 institutions in 1 country.

Chao Li *Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.ORCID 0000-0001-9768-4004
Zhishuang Gao *Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Zhiwei Cui *Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.ORCID 0000-0003-1362-435X
Zonghang LiuDepartment of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Yibo BianDepartment of Oncology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Haoyu SunDepartment of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Nuofan WangDepartment of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Zhongyuan HeDepartment of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Bowen LiDepartment of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Fengyuan LiDepartment of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Zheng LiDepartment of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Linjun WangDepartment of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Diancai ZhangDepartment of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Li YangDepartment of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Zekuan XuDepartment of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. xuzekuan@njmu.edu.cn.ORCID 0000-0001-5179-4128
Hao XuDepartment of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. hxu@njmu.edu.cn.ORCID 0000-0001-5827-1821
Jiangsu Cancer Hospital · CNSecond Affiliated Hospital of Nanjing Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Imatinib is a tyrosine kinase inhibitor that is widely used to combat gastrointestinal stromal tumours (GISTs). However, secondary resistance to imatinib is an important challenge in GIST treatment. Recent studies have demonstrated that cancer-derived nanosized exosomes play a key role in intercellular communication, but little is known about the roles of exosomes in imatinib-resistant GISTs. Here, we reveal that exosomes released from imatinib-resistant GISTs transmit drug resistance to imatinib-sensitive tumours. By using iTRAQ technology, we demonstrate that Ras-related protein Rab-35 (Rab35) is upregulated differentially in imatinib-resistant GISTs. Loss of Rab35 decreases exosome secretion, thereby hampering the transmission of imatinib resistance to sensitive tumours. Mechanistically, we showed that the ubiquitin‒proteasome system is involved in elevated Rab35 expression and that ubiquitin-specific protease 32 (USP32), a deubiquitylating enzyme, is bound to Rab35. Further experiments demonstrate that this protease protects Rab35 from proteasomal degradation by reducing Lys48 (K48)-ubiquitination. Additionally, we found that the transcription factor ETV1, which is a lineage survival factor in GISTs, promotes USP32 expression. Collectively, our results reveal that exosomes transmit imatinib resistance in GISTs and that deubiquitylation plays a key role in regulating the transmission process. The USP32-Rab35 axis provides a potential target for interventions to reduce the occurrence of imatinib resistance in GISTs.

Indexed as

Antineoplastic AgentsExosomesGastrointestinal Stromal TumorsDrug Resistance, NeoplasmHumansImatinib MesylateProto-Oncogene Proteins c-kitPyrimidinesrab GTP-Binding ProteinsAntineoplastic AgentsImatinib MesylateProto-Oncogene Proteins c-kitPyrimidinesRAB35 protein, humanrab GTP-Binding Proteins

Identifiers

PMID36725886
OpenAlexW4318817299

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.