Browsing by Subject "Asymmetric division"

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    EGFL6 regulates the asymmetric division, maintenance and metastasis of ALDH+ ovarian cancer cells
    (American Association for Cancer Research, 2016-11-01) Bai, Shoumei; Ingram, Patrick; Chen, Yu-Chih; Deng, Ning; Pearson, Alex; Niknafs, Yashar; O'Hayer, Patrick; Wang, Yun; Zhang, Zhong-Yin; Boscolo, Elisa; Bischoff, Joyce; Yoon, Euisik; Buckanovich, Ronald J; Biochemistry and Molecular Biology, School of Medicine
    Little 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.