Pancreatic tumor cell metastasis is restricted by MT1-MMP binding protein MTCBP-1.
Animals
Cell Line, Tumor
Cell Movement
Cell Proliferation
Dioxygenases
/ antagonists & inhibitors
Gene Expression Regulation, Neoplastic
Humans
Intestinal Neoplasms
/ genetics
Intestine, Small
/ metabolism
Lymphatic Metastasis
Matrix Metalloproteinase 14
/ genetics
Mice
Mice, Nude
Neoplasm Invasiveness
Pancreas
/ metabolism
Pancreatic Neoplasms
/ genetics
Podosomes
/ genetics
Protein Binding
RNA, Small Interfering
/ genetics
Signal Transduction
Survival Analysis
Xenograft Model Antitumor Assays
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
07 01 2019
07 01 2019
Historique:
received:
07
02
2018
revised:
28
09
2018
accepted:
29
10
2018
pubmed:
30
11
2018
medline:
23
10
2019
entrez:
30
11
2018
Statut:
ppublish
Résumé
The process by which tumor cells mechanically invade through surrounding stroma into peripheral tissues is an essential component of metastatic dissemination. The directed recruitment of the metalloproteinase MT1-MMP to invadopodia plays a critical role in this invasive process. Here, we provide mechanistic insight into MT1-MMP cytoplasmic tail binding protein 1 (MTCBP-1) with respect to invadopodia formation, matrix remodeling, and invasion by pancreatic tumor cells. MTCBP-1 localizes to invadopodia and interacts with MT1-MMP. We find that this interaction displaces MT1-MMP from invadopodia, thereby attenuating their number and function and reducing the capacity of tumor cells to degrade matrix. Further, we observe an inverse correlation between MTCBP-1 and MT1-MMP expression both in cultured cell lines and human pancreatic tumors. Consistently, MTCBP-1-expressing cells show decreased ability to invade in vitro and metastasize in vivo. These findings implicate MTCBP-1 as an inhibitor of the metastatic process.
Identifiants
pubmed: 30487181
pii: jcb.201802032
doi: 10.1083/jcb.201802032
pmc: PMC6314558
doi:
Substances chimiques
RNA, Small Interfering
0
ADI1 protein, human
EC 1.-
Dioxygenases
EC 1.13.11.-
MMP14 protein, human
EC 3.4.24.80
Matrix Metalloproteinase 14
EC 3.4.24.80
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
317-332Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK084567
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA102701
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA104125
Pays : United States
Informations de copyright
© 2018 Qiang et al.
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