Evidence map›Paper›PMID 42377994›Full record

ArticleJournal of extracellular vesicles2026

Silencing the Signal: The Metastasis Suppressor NDRG1 Disrupts Small Extracellular Vesicle-Mediated Crosstalk in Pancreatic Cancer.

Jiawei Chang, Shafi Alenizi, Heloisa Zaccaron Milioli, Winston Lay, Saranya Pounraj, Yujie Li, Mekonnen Sisay Shiferaw, Elham Hosseini-Beheshti, Zaklina Kovacevic

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of extracellular vesicles, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Jiawei ChangDepartment of Physiology, School of Biomedical Sciences, Faculty of Medicine and Health, University of NSW, Sydney, Australia.
Shafi AleniziDepartment of Physiology, School of Biomedical Sciences, Faculty of Medicine and Health, University of NSW, Sydney, Australia.
Heloisa Zaccaron MilioliGarvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
Winston LayAsbestos and Dust Disease Research Institute (ADDRI), Sydney, New South Wales, Australia.
Saranya PounrajDepartment of Physiology, School of Biomedical Sciences, Faculty of Medicine and Health, University of NSW, Sydney, Australia.
Yujie LiDepartment of Physiology, School of Biomedical Sciences, Faculty of Medicine and Health, University of NSW, Sydney, Australia.ORCID https://orcid.org/0000-0001-7597-9741
Mekonnen Sisay ShiferawDepartment of Physiology, School of Biomedical Sciences, Faculty of Medicine and Health, University of NSW, Sydney, Australia.ORCID https://orcid.org/0000-0001-6611-1174
Elham Hosseini-BeheshtiSchool of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Zaklina KovacevicDepartment of Physiology, School of Biomedical Sciences, Faculty of Medicine and Health, University of NSW, Sydney, Australia.ORCID https://orcid.org/0000-0002-4742-4690

Funding

National Health and Medical Research Council of Australia 2019552Pankind Australian Pancreatic Cancer Foundation (2022 Innovation Grant)
6 · The paper itself

Abstract

Pancreatic cancer (PaC) remains one of the deadliest cancers, with 5-year survival rates of 13%. A major driver of its aggressiveness is the tumour microenvironment (TME), which fuels tumour growth, metastasis, and therapeutic resistance through dynamic, bi-directional communication between cancer cells, fibroblasts, and immune cells. Emerging evidence highlights extracellular vesicles (EVs) as key mediators of oncogenic cross-talk within the PaC TME. This study demonstrates for the first time that the overexpression of metastasis suppressor N-myc downstream regulated gene 1 (NDRG1) significantly influences the biogenesis, cargo packaging and release of EVs by cancer cells. This was mediated by a direct interaction between NDRG1 and ALIX, a key protein involved in EV biogenesis and packaging, with NDRG1 facilitating ALIX proteasomal degradation. Further, EVs released from NDRG1-overexpressing cells had significantly fewer CAF-activation proteins (i.e. TGF-β), leading to attenuated ERK1/2 and p38 activation in pancreatic stellate cells (PSCs), and reduced expression of key fibrotic markers (α-SMA, FAP, and collagen 1A). NDRG1 overexpression also reduced sEVs uptake by PaC cells and diverted these to the lysosome for degradation. These findings uncover a previously unrecognized mechanism by which NDRG1 overexpression disrupts the oncogenic two-way communication between PaC cells and the TME, positioning NDRG1 overexpression as a compelling therapeutic approach against this formidable malignancy.

Indexed as

Cell Cycle ProteinsExtracellular VesiclesIntracellular Signaling Peptides and ProteinsPancreatic NeoplasmsAnimalsCalcium-Binding ProteinsCell Line, TumorEndosomal Sorting Complexes Required for TransportHumansN-myc Downstream-Regulated Gene 1 ProteinPancreatic Stellate CellsSignal TransductionTumor MicroenvironmentCalcium-Binding ProteinsCell Cycle ProteinsEndosomal Sorting Complexes Required for TransportIntracellular Signaling Peptides and ProteinsN-myc Downstream-Regulated Gene 1 ProteinPDCD6IP protein, humanALIXESCRT pathwayNDRG1pancreatic cancersEVstumour microenvironment

Identifiers

PMID42377994
PMCPMC13317765

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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.