TY - JOUR
T1 - EGFL6 regulates the asymmetric division, maintenance, and metastasis of ALDH+ ovarian cancer cells
AU - Bai, Shoumei
AU - Ingram, Patrick
AU - Chen, Yu Chih
AU - Deng, Ning
AU - Pearson, Alex
AU - Niknafs, Yashar
AU - O'Hayer, Patrick
AU - Wang, Yun
AU - Zhang, Zhong Yin
AU - Boscolo, Elisa
AU - Bischoff, Joyce
AU - Yoon, Euisik
AU - Buckanovich, Ronald J.
N1 - Publisher Copyright:
© 2016 AACR.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Little is known about the factors that regulate the asymmetric division of cancer stem-like cells (CSC).Here,we demonstrate that EGFL6, a stem cell regulatory factor expressed in ovarian tumor cells and vasculature, regulates ALDH+ ovarian 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. Cancer Res; 76(21); 6396-409.
AB - Little is known about the factors that regulate the asymmetric division of cancer stem-like cells (CSC).Here,we demonstrate that EGFL6, a stem cell regulatory factor expressed in ovarian tumor cells and vasculature, regulates ALDH+ ovarian 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. Cancer Res; 76(21); 6396-409.
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U2 - 10.1158/0008-5472.CAN-16-0225
DO - 10.1158/0008-5472.CAN-16-0225
M3 - Article
C2 - 27803106
AN - SCOPUS:84996561870
SN - 0008-5472
VL - 76
SP - 6396
EP - 6409
JO - Cancer Research
JF - Cancer Research
IS - 21
ER -
