Evidence map›Paper›PMID 25732677›Full record

ArticleCell research2015

Heparanase activates the syndecan-syntenin-ALIX exosome pathway.

Bart Roucourt, Sofie Meeussen, Jie Bao, Pascale Zimmermann, Guido David

Open access · hybridAbstract read
In one paragraph

Article in Cell research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 199 papers.

0numbers the graph read from it
0cells of the map it votes in
199citing papers in PubMed
14.8field-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

199 citing papers in PubMed, 313 citations in OpenAlex.

  1. Biology and Therapeutic Potential of Exosomes, Targeted Drug Delivery.International journal of molecular sciences · 2026
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139 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Bart Roucourt1] Laboratory for Glycobiology and Developmental Genetics, Department of Human Genetics, KU Leuven, Leuven, B-3000, Belgium [2] Laboratory for Signal Integration in Cell Fate Decision, Department of Human Genetics, KU Leuven, Leuven, B-3000, Belgium.
Sofie Meeussen1] Laboratory for Glycobiology and Developmental Genetics, Department of Human Genetics, KU Leuven, Leuven, B-3000, Belgium [2] Laboratory for Signal Integration in Cell Fate Decision, Department of Human Genetics, KU Leuven, Leuven, B-3000, Belgium.
Jie Bao1] Laboratory for Glycobiology and Developmental Genetics, Department of Human Genetics, KU Leuven, Leuven, B-3000, Belgium [2] Laboratory for Signal Integration in Cell Fate Decision, Department of Human Genetics, KU Leuven, Leuven, B-3000, Belgium.
Pascale Zimmermann1] Laboratory for Signal Integration in Cell Fate Decision, Department of Human Genetics, KU Leuven, Leuven, B-3000, Belgium [2] Centre de Recherche en Cancérologie de Marseille (CRCM), Aix-Marseille Université, Marseille, F-13284, France; Inserm, U1068; Institut Paoli-Calmettes; CNRS, UMR7258, Marseille, F-13009, France.
Guido DavidLaboratory for Glycobiology and Developmental Genetics, Department of Human Genetics, KU Leuven, Leuven, B-3000, Belgium.
KU Leuven · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Exosomes are secreted vesicles of endosomal origin involved in signaling processes. We recently showed that the syndecan heparan sulfate proteoglycans control the biogenesis of exosomes through their interaction with syntenin-1 and the endosomal-sorting complex required for transport accessory component ALIX. Here we investigated the role of heparanase, the only mammalian enzyme able to cleave heparan sulfate internally, in the syndecan-syntenin-ALIX exosome biogenesis pathway. We show that heparanase stimulates the exosomal secretion of syntenin-1, syndecan and certain other exosomal cargo, such as CD63, in a concentration-dependent manner. In contrast, exosomal CD9, CD81 and flotillin-1 are not affected. Conversely, reduction of endogenous heparanase reduces the secretion of syntenin-1-containing exosomes. The ability of heparanase to stimulate exosome production depends on syntenin-1 and ALIX. Syndecans, but not glypicans, support exosome biogenesis in heparanase-exposed cells. Finally, heparanase stimulates intraluminal budding of syndecan and syntenin-1 in endosomes, depending on the syntenin-ALIX interaction. Taken together, our findings identify heparanase as a modulator of the syndecan-syntenin-ALIX pathway, fostering endosomal membrane budding and the biogenesis of exosomes by trimming the heparan sulfate chains on syndecans. In addition, our data suggest that this mechanism controls the selection of specific cargo to exosomes.

Indexed as

Calcium-Binding ProteinsCell Cycle ProteinsEndosomal Sorting Complexes Required for TransportExosomesGene Expression RegulationGene Knockdown TechniquesGlucuronidaseHeparanaseHeparan SulfateHumansMCF-7 CellsMembrane ProteinsSignal TransductionSyndecansSynteninsCalcium-Binding ProteinsCell Cycle ProteinsEndosomal Sorting Complexes Required for TransportflotillinsGlucuronidaseHeparanaseHeparan SulfateMembrane ProteinsPDCD6IP protein, humanSyndecansSyntenins

Identifiers

PMID25732677
PMCPMC4387558
OpenAlexW2077882252

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.