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.