| Item type |
文献 / Documents(1) |
| 公開日 |
2020-10-29 |
| アクセス権 |
|
|
アクセス権 |
open access |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版社版DOI |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.3390/cancers12040881 |
|
|
言語 |
ja |
|
|
関連名称 |
10.3390/cancers12040881 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
|
|
タイトル |
Extracellular Vesicles Enriched with Moonlighting Metalloproteinase Are Highly Transmissive, Pro-Tumorigenic, and Trans-Activates Cellular Communication Network Factor (CCN2/CTGF) : CRISPR against Cancer |
|
言語 |
en |
| 著者 |
オクシャ, ユカ
エグチ, タカノリ
Tran, Manh T.
ソガワ, チハル
吉田, 賀弥
イタガキ, マミ
Taha, Eman A.
オノ, キショウ
アオヤマ, エリコ
岡村, 裕彦
コザキ, ケンイチ
Calderwood, Stuart K.
タキガワ, マサハル
オカモト, クニアキ
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
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 CCN2/CTGF promoter, and induced CCN2/CTGF production in vitro. TRENDIC and other cis-elements in the CCN2/CTGF promoter were essential for the oncosomal responsivity. The CRISPR/Cas9-mediated knockout of MMP3 showed significant anti-tumor effects such as the inhibition of migration and invasion of tumor cells, and a reduction in CCN2/CTGF promoter activity and fragmentations in vitro. A high expression level of MMP3 or CCN2/CTGF mRNA was prognostic and unfavorable in particular types of cancers including head and neck, lung, pancreatic, cervical, stomach, and urothelial cancers. These data newly demonstrate that oncogenic EVs-derived MMP is a transmissive trans-activator for the cellular communication network gene and promotes tumorigenesis at distant sites. |
|
言語 |
en |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
matrix metalloproteinase |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
moonlighting metalloproteinase (MMP) |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
protein moonlighting |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
transcription factor |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
extracellular vesicles |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
oncosome |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
genome editing |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
CRISPR |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
cellular communication network factor |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
CCN2/CTGF |
| 書誌情報 |
en : Cancers
巻 12,
号 4,
p. 881,
発行日 2020-04-04
|
| 収録物ID |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
20726694 |
| 出版者 |
|
|
出版者 |
MDPI |
|
言語 |
en |
| 権利情報 |
|
|
言語 |
en |
|
権利情報 |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
| EID |
|
|
識別子 |
365396 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
cancers_12_4_881.pdf (4.25 MB)
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