SNX9 determines the surface levels of integrin β1 in vascular endothelial cells: Implication in poor prognosis of human colorectal cancers overexpressing SNX9.
Angiogenesis Inducing Agents
/ metabolism
Cell Membrane
/ metabolism
Cell Movement
/ physiology
Cell Proliferation
/ physiology
Colorectal Neoplasms
/ metabolism
Human Umbilical Vein Endothelial Cells
/ metabolism
Humans
Integrin beta1
/ metabolism
Integrins
/ metabolism
Neovascularization, Pathologic
/ genetics
Protein Transport
/ physiology
Sorting Nexins
/ metabolism
angiogenesis
colorectal cancer
endothelial cells
integrin β1
sorting nexin 9
Journal
Journal of cellular physiology
ISSN: 1097-4652
Titre abrégé: J Cell Physiol
Pays: United States
ID NLM: 0050222
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
26
11
2018
revised:
31
01
2019
accepted:
01
02
2019
pubmed:
21
2
2019
medline:
2
6
2020
entrez:
21
2
2019
Statut:
ppublish
Résumé
Angiogenesis, the formation of new blood vessels, is involved in a variety of diseases including the tumor growth. In response to various angiogenic stimulations, a number of proteins on the surface of vascular endothelial cells are activated to coordinate cell proliferation, migration, and spreading processes to form new blood vessels. Plasma membrane localization of these angiogenic proteins, which include vascular endothelial growth factor receptors and integrins, are warranted by intracellular membrane trafficking. Here, by using a siRNA library, we screened for the sorting nexin family that regulates intracellular trafficking and identified sorting nexin 9 (SNX9) as a novel angiogenic factor in human umbilical vein endothelial cells (HUVECs). SNX9 was essential for cell spreading on the Matrigel, and tube formation that mimics in vivo angiogenesis in HUVECs. SNX9 depletion significantly delayed the recycling of integrin β1, an essential adhesion molecule for angiogenesis, and reduced the surface levels of integrin β1 in HUVECs. Clinically, we showed that SNX9 protein was highly expressed in tumor endothelial cells of human colorectal cancer tissues. High-level expression of SNX9 messenger RNA significantly correlated with poor prognosis of the patients with colorectal cancer. These results suggest that SNX9 is an angiogenic factor and provide a novel target for the development of new antiangiogenic drugs.
Identifiants
pubmed: 30784076
doi: 10.1002/jcp.28346
pmc: PMC6617759
doi:
Substances chimiques
Angiogenesis Inducing Agents
0
Integrin beta1
0
Integrins
0
Itgb1 protein, human
0
SNX9 protein, human
0
Sorting Nexins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
17280-17294Informations de copyright
© 2019 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.
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