Extracellular Vesicles Enriched with Moonlighting Metalloproteinase Are Highly Transmissive, Pro-Tumorigenic, and Trans-Activates Cellular Communication Network Factor (
CCN2/CTGF
CRISPR
cellular communication network factor
extracellular vesicles
genome editing
matrix metalloproteinase
moonlighting metalloproteinase (MMP)
oncosome
protein moonlighting
transcription factor
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
04 Apr 2020
04 Apr 2020
Historique:
received:
19
02
2020
revised:
24
03
2020
accepted:
02
04
2020
entrez:
9
4
2020
pubmed:
9
4
2020
medline:
9
4
2020
Statut:
epublish
Résumé
Matrix metalloproteinase 3 (MMP3) plays multiple roles in extracellular proteolysis as well as intracellular transcription, prompting a new definition of moonlighting metalloproteinase (MMP), according to a definition of protein moonlighting (or gene sharing), a phenomenon by which a protein can perform more than one function. Indeed, connective tissue growth factor (CTGF, aka cellular communication network factor 2 (CCN2)) is transcriptionally induced as well as cleaved by MMP3. Moreover, several members of the MMP family have been found within tumor-derived extracellular vesicles (EVs). We here investigated the roles of MMP3-rich EVs in tumor progression, molecular transmission, and gene regulation. EVs derived from a rapidly metastatic cancer cell line (LuM1) were enriched in MMP3 and a C-terminal half fragment of CCN2/CTGF. MMP3-rich, LuM1-derived EVs were disseminated to multiple organs through body fluid and were pro-tumorigenic in an allograft mouse model, which prompted us to define LuM1-EVs as oncosomes in the present study. Oncosome-derived MMP3 was transferred into recipient cell nuclei and thereby trans-activated the
Identifiants
pubmed: 32260433
pii: cancers12040881
doi: 10.3390/cancers12040881
pmc: PMC7226423
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Japan Society for the Promotion of Science
ID : JP17K17895
Organisme : Japan Society for the Promotion of Science
ID : JP17K11642
Organisme : Japan Society for the Promotion of Science
ID : JP19H03817
Organisme : Japan Society for the Promotion of Science
ID : 19H04051
Organisme : Japan Society for the Promotion of Science
ID : JP17K11643
Organisme : Japan Society for the Promotion of Science
ID : 17K11669
Organisme : Japan Society for the Promotion of Science
ID : 18K09789
Organisme : Suzuken Memorial Foundation
ID : TE
Organisme : Ryobi Teien Memory Foundation
ID : KOk, CS, TE
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