Evidence map›Paper›PMID 35637408›Full record

ArticleNature cell biology2022

Cancer-cell-secreted extracellular vesicles suppress insulin secretion through miR-122 to impair systemic glucose homeostasis and contribute to tumour growth.

Minghui Cao, Roi Isaac, Wei Yan, Xianhui Ruan, Li Jiang, Yuhao Wan, Jessica Wang, Emily Wang, Christine Caron, Steven Neben and 19 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
11.0field-weighted citation impact, top 1% 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

82 citing papers in PubMed, 128 citations in OpenAlex.

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  18. Extracellular vesicles in preeclampsia: drivers of vascular dysfunction and inflammation.American journal of physiology. Heart and circulatory physiology · 2025
    Review
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22 more citing papers are in PubMed but not listed here.

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

29 authors at 4 institutions in 1 country.

Minghui CaoDepartment of Pathology, University of California, San Diego, La Jolla, CA, USA.
Roi IsaacDepartment of Medicine, University of California, San Diego, La Jolla, CA, USA.
Wei YanDepartment of Pathology, University of California, San Diego, La Jolla, CA, USA.
Xianhui RuanDepartment of Pathology, University of California, San Diego, La Jolla, CA, USA.
Li JiangDepartment of Pathology, University of California, San Diego, La Jolla, CA, USA.
Yuhao WanDepartment of Pathology, University of California, San Diego, La Jolla, CA, USA.
Jessica WangDepartment of Pathology, University of California, San Diego, La Jolla, CA, USA.
Emily WangDepartment of Pathology, University of California, San Diego, La Jolla, CA, USA.
Christine CaronDepartment of Pathology, University of California, San Diego, La Jolla, CA, USA.
Steven NebenRegulus Therapeutics Inc., San Diego, CA, USA.
Denis DryginRegulus Therapeutics Inc., San Diego, CA, USA.
Donald P PizzoDepartment of Pathology, University of California, San Diego, La Jolla, CA, USA.
Xiwei WuDepartment of Molecular and Cellular Biology, City of Hope, Duarte, CA, USA.
Xuxiang LiuDepartment of Pathology, University of California, San Diego, La Jolla, CA, USA.
Andrew R ChinDepartment of Pathology, University of California, San Diego, La Jolla, CA, USA.
Miranda Y FongDepartment of Pathology, University of California, San Diego, La Jolla, CA, USA.
Ziting GaoDepartment of Chemistry, University of California, Riverside, Riverside, CA, USA.
Kaizhu GuoDepartment of Chemistry, University of California, Riverside, Riverside, CA, USA.
Oluwole FadareDepartment of Pathology, University of California, San Diego, La Jolla, CA, USA.
Richard B SchwabDepartment of Medicine, University of California, San Diego, La Jolla, CA, USA.
Yuan YuanDepartment of Medical Oncology & Therapeutics Research, City of Hope, Duarte, CA, USA.
Susan E YostDepartment of Medical Oncology & Therapeutics Research, City of Hope, Duarte, CA, USA.
Joanne MortimerDepartment of Medical Oncology & Therapeutics Research, City of Hope, Duarte, CA, USA.
Wenwan ZhongDepartment of Chemistry, University of California, Riverside, Riverside, CA, USA.
Wei YingDepartment of Medicine, University of California, San Diego, La Jolla, CA, USA.
Jack D BuiDepartment of Pathology, University of California, San Diego, La Jolla, CA, USA.
Dorothy D SearsDepartment of Medicine, University of California, San Diego, La Jolla, CA, USA.
Jerrold M OlefskyDepartment of Medicine, University of California, San Diego, La Jolla, CA, USA.
Shizhen Emily WangDepartment of Pathology, University of California, San Diego, La Jolla, CA, USA. emilywang@ucsd.edu.ORCID http://orcid.org/0000-0002-5036-8175
University of California San Diego · USCity of Hope · USUniversity of California, Riverside · USRegulus Therapeutics (United States) · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jesse Nodora · 1985 to 2026
$124.9M
Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI XIWEI WU · 1985 to 2026
$86.3M
(PQA4) GPS exposure to environments & relations with biomarkers of cancer riskR01CA179977 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KERR, JACQUELINE · 2013 to 2016
$3.0M
Role of breast cancer-secreted miRNA in directing a stromal metabolic plasticityR01CA218140 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WANG, SHIZHEN EMILY · 2017 to 2021
$2.4M
Targeting Chemotherapy-induced Breast Cancer StemnessR01CA206911 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WANG, SHIZHEN EMILY, YUAN, YUAN · 2017 to 2021
$2.3M
Role of breast cancer secreted miRNA in brain metastasisR01CA266486 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Shizhen Emily Wang · 2022 to 2026
$2.2M
JEOL JEM-1400Plus Transmission Electron MicroscopeS10OD023527 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FARQUHAR, MARILYN GIST · 2017 to 2017
$579k
NCI NIH HHS P30 CA023100NCI NIH HHS P30 CA033572NCI NIH HHS R01 CA179977NCI NIH HHS R01 CA206911NCI NIH HHS R01 CA218140NCI NIH HHS R01 CA266486NIH HHS S10 OD023527
6 · The paper itself

Abstract

Epidemiological studies demonstrate an association between breast cancer (BC) and systemic dysregulation of glucose metabolism. However, how BC influences glucose homeostasis remains unknown. We show that BC-derived extracellular vesicles (EVs) suppress pancreatic insulin secretion to impair glucose homeostasis. EV-encapsulated miR-122 targets PKM in β-cells to suppress glycolysis and ATP-dependent insulin exocytosis. Mice receiving high-miR-122 EVs or bearing BC tumours exhibit suppressed insulin secretion, enhanced endogenous glucose production, impaired glucose tolerance and fasting hyperglycaemia. These effects contribute to tumour growth and are abolished by inhibiting EV secretion or miR-122, restoring PKM in β-cells or supplementing insulin. Compared with non-cancer controls, patients with BC have higher levels of circulating EV-encapsulated miR-122 and fasting glucose concentrations but lower fasting insulin; miR-122 levels are positively associated with glucose and negatively associated with insulin. Therefore, EV-mediated impairment of whole-body glycaemic control may contribute to tumour progression and incidence of type 2 diabetes in some patients with BC.

Indexed as

Breast NeoplasmsDiabetes Mellitus, Type 2Extracellular VesiclesMicroRNAsAnimalsFemaleGlucoseHomeostasisHumansInsulinInsulin SecretionMiceGlucoseInsulinMicroRNAsMIRN122 microRNA, humanMirn122 microRNA, mouse

Identifiers

PMID35637408
PMCPMC9233030
OpenAlexW4281669454

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.