Epithin/PRSS14 proteolytically regulates angiopoietin receptor Tie2 during transendothelial migration.

Abstract:

:Epithin/PRSS14, a type II transmembrane serine protease, is involved in normal epithelial development and tumor progression. Here we report, as an interacting substrate of epithin, a receptor tyrosine kinase Tie2 that is well known for important roles in the vessel stability. Epithin interacts with and degrades the Tie2 extracellular portion that contains the ligand-binding domain. Epithin is located in the neighbor of Tie2-expressing vessels in normal tissue. Furthermore, epithin can cleave and degrade Tie2 not only in the same cell but also from neighboring cells nearby, resulting in the degradation of the Tie2 ectodomain. The remaining Tie2 fragment was highly phosphorylated and was able to recruit a downstream effector, phosphatidylinositol 3-kinase. Knocking down epithin expression using short hairpin RNA in thymoma cell severely impaired the migration through endothelial cells that show the actin rearrangement during the process. The diminution of epithin protein expression in 4T1 breast cancer cells caused the significant decrease in the number of transendothelial migrating cells in vitro as well as in those of metastasizing tumor nodules in vivo, Therefore, we propose that epithin, which regulates endothelial Tie2 functions, plays a critical role in the fine tuning of transendothelial migration for normal and cancer cells.

journal_name

Blood

journal_title

Blood

authors

Kim C,Lee HS,Lee D,Lee SD,Cho EG,Yang SJ,Kim SB,Park D,Kim MG

doi

10.1182/blood-2010-03-275289

subject

Has Abstract

pub_date

2011-01-27 00:00:00

pages

1415-24

issue

4

eissn

0006-4971

issn

1528-0020

pii

blood-2010-03-275289

journal_volume

117

pub_type

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