EGFL6 promotes endometrial cancer cell migration and proliferation

Alison A Garrett; Shoumei Bai; Sandra Cascio; Navneet Gupta; Dongli Yang; Ronald J Buckanovich

doi:10.1016/j.ygyno.2024.02.016

EGFL6 promotes endometrial cancer cell migration and proliferation

Gynecol Oncol. 2024 Feb 17:185:75-82. doi: 10.1016/j.ygyno.2024.02.016. Online ahead of print.

Authors

Alison A Garrett¹, Shoumei Bai¹, Sandra Cascio¹, Navneet Gupta¹, Dongli Yang², Ronald J Buckanovich³

Affiliations

¹ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, UPMC Hillman Cancer Center and the Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA.
² Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, UPMC Hillman Cancer Center and the Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
³ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, UPMC Hillman Cancer Center and the Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: buckanovichrj@mwri.magee.edu.

PMID: 38368816
DOI: 10.1016/j.ygyno.2024.02.016

Abstract

Objective: EGFL6, a growth factor produced by adipocytes, is upregulated in and implicated in the tumorigenesis of multiple tumor types. Given the strong link between obesity and endometrial cancer, we sought to determine the impact of EGFL6 on endometrial cancer.

Methods: EGFL6 expression in endometrial cancer and correlation with patient outcomes was evaluated in the human protein atlas and TCGA. EGFL6 treatment, expression upregulation, and shRNA knockdown were used to evaluate the impact of EGFL6 on the proliferation and migration of 3 endometrial cancer cell lines in vitro. Similarly, the impact of EGFL6 expression and knockdown on tumor growth was evaluated. Western blotting was used to evaluate the impact of EGFL6 on MAPK phosphorylation.

Results: EGFL6 is upregulated in endometrial cancer, primarily in cony-number high tumors. High tumor endometrial cancer expression of EGFL6 predicts poor patient prognosis. We find that EGFL6 acts to activate the MAPK pathway increasing cellular proliferation and migration. In xenograft models, EGFL6 overexpression increases endometrial cancer tumor growth while EGFL6 knockdown decreases endometrial cancer tumor growth.

Conclusions: EGFL6 is a marker of poor prognosis endometrial cancers, driving cancer cell proliferation and growth. As such EGFL6 represents a potential therapeutic target in endometrial cancer.

Keywords: EGFL6; Endometrial cancer; MAPK.