EGFL6 regulates the asymmetric division, maintenance, and metastasis of ALDH+ ovarian cancer cells

Shoumei Bai, Patrick Ingram, Yu Chih Chen, Ning Deng, Alex Pearson, Yashar Niknafs, Patrick O'Hayer, Yun Wang, Zhong Yin Zhang, Elisa Boscolo, Joyce Bischoff, Euisik Yoon, Ronald J. Buckanovich

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)6396-6409
Number of pages14
JournalCancer Research
Volume76
Issue number21
DOIs
Publication statusPublished - 2016 Nov 1

Fingerprint

Ovarian Neoplasms
Maintenance
Neoplastic Stem Cells
Neoplasm Metastasis
Neoplasms
Growth
Stem Cell Factor
Oncogene Proteins
Neutralizing Antibodies
Ovary
Cell Count
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Bai, 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-16-0225
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. / EGFL6 regulates the asymmetric division, maintenance, and metastasis of ALDH+ ovarian cancer cells. In: Cancer Research. 2016 ; Vol. 76, No. 21. pp. 6396-6409.
@article{3e18d58b72e1463ba6a6f39aef3963fe,
title = "EGFL6 regulates the asymmetric division, maintenance, and metastasis of ALDH+ ovarian cancer cells",
abstract = "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.",
author = "Shoumei Bai and Patrick Ingram and Chen, {Yu Chih} and Ning Deng and Alex Pearson and Yashar Niknafs and Patrick O'Hayer and Yun Wang and Zhang, {Zhong Yin} and Elisa Boscolo and Joyce Bischoff and Euisik Yoon and Buckanovich, {Ronald J.}",
year = "2016",
month = "11",
day = "1",
doi = "10.1158/0008-5472.CAN-16-0225",
language = "English",
volume = "76",
pages = "6396--6409",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "21",

}

Bai, S, Ingram, P, Chen, YC, Deng, N, Pearson, A, Niknafs, Y, O'Hayer, P, Wang, Y, Zhang, ZY, Boscolo, E, Bischoff, J, Yoon, E & Buckanovich, RJ 2016, 'EGFL6 regulates the asymmetric division, maintenance, and metastasis of ALDH+ ovarian cancer cells', Cancer Research, vol. 76, no. 21, pp. 6396-6409. https://doi.org/10.1158/0008-5472.CAN-16-0225

EGFL6 regulates the asymmetric division, maintenance, and metastasis of ALDH+ ovarian cancer cells. / 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.

In: Cancer Research, Vol. 76, No. 21, 01.11.2016, p. 6396-6409.

Research output: Contribution to journalArticle

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.

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.

UR - http://www.scopus.com/inward/record.url?scp=84996561870&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84996561870&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-16-0225

DO - 10.1158/0008-5472.CAN-16-0225

M3 - Article

C2 - 27803106

AN - SCOPUS:84996561870

VL - 76

SP - 6396

EP - 6409

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 21

ER -