Bai, ShoumeiIngram, PatrickChen, Yu-ChihDeng, NingPearson, AlexNiknafs, YasharO'Hayer, PatrickWang, YunZhang, Zhong-YinBoscolo, ElisaBischoff, JoyceYoon, EuisikBuckanovich, Ronald J2018-05-102018-05-102016-11-01Bai, S., Ingram, P., Chen, Y.-C., Deng, N., Pearson, A., Niknafs, Y., … Buckanovich, R. J. (2016). EGFL6 regulates the asymmetric division, maintenance and metastasis of ALDH+ ovarian cancer cells. Cancer Research, 76(21), 6396–6409. https://doi.org/10.1158/0008-5472.CAN-16-02250008-5472https://hdl.handle.net/1805/16129Little is known about the factors that regulate the asymmetric division of cancer stem-like cells. Here we demonstrate that EGFL6, a stem cell regulatory factor expressed in ovarian tumor cells and vasculature, regulates ALDH+ ovarian cancer stem-like cells (CSC). EGFL6 signaled at least in part via the oncoprotein SHP2 with concomitant activation of ERK. EGFL6 signaling promoted the migration and asymmetric division of ALDH+ ovarian CSC. As such, EGFL6 increased not only tumor growth but also metastasis. Silencing of EGFL6 or SHP2 limited numbers of ALDH+ cells and reduced tumor growth, supporting a critical role for EGFL6/SHP2 in ALDH+ cell maintenance. Notably, systemic administration of an EGFL6-neutralizing antibody we generated restricted tumor growth and metastasis, specifically blocking ovarian cancer cell recruitment to the ovary. Together, our results offer a preclinical proof of concept for EGFL6 as a novel therapeutic target for the treatment of ovarian cancer.en-USPublisher PolicyEGFL6SHP2Cancer Stem-like cellTumor endothelial cellOvarian CancerAsymmetric divisionArticle