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31 May 2018 Autophagy contributes to hypoxia-induced epithelial to mesenchymal transition of endometrial epithelial cells in endometriosis
Hengwei Liu, Yu Du, Zhibing Zhang, Liqun Lv, Wenqian Xiong, Ling Zhang, Na Li, Haitang He, Qi Li, Yi Liu
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Abstract

Endometriosis is a benign gynecologic disorder, and presents with malignant characteristics, such as migration and invasion. Hypoxia has been implicated in triggering epithelial–mesenchymal transition (EMT). Hypoxia is also known to induce autophagy. However, the relationship between autophagy and EMT under hypoxia conditions in endometriosis remains unknown. In the present study, we found that the expression of hypoxia-inducible factor-1α (HIF-1α), microtubule associated protein light chain 3 (LC3), and mesenchymal cell marker vimentin was significantly higher in ectopic endometrium from patients with endometriosis, along with decreased expression of epithelial cell marker E-cadherin. After hypoxia treatment, endometrial epithelial cells exhibited enhanced migration and invasion abilities, as well as promoted autophagy and the EMT phenotype. Our analyses also show that HIF-1α was responsible for induction of autophagy. Moreover, inhibition of autophagy by chemical or genetic approaches suppressed hypoxia triggered EMT and reduced cell migration and invasion. Collectively, our findings identify that autophagy is critical for the migration and invasion of endometrial cells through the induction of EMT and indicate that inhibition of autophagy may be a novel useful strategy in the treatment of endometriosis.

Summary Sentence

The autophagy, which is induced by peritoneal hypoxia, is essential for EMT initiation in endometriosis.

© The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Hengwei Liu, Yu Du, Zhibing Zhang, Liqun Lv, Wenqian Xiong, Ling Zhang, Na Li, Haitang He, Qi Li, and Yi Liu "Autophagy contributes to hypoxia-induced epithelial to mesenchymal transition of endometrial epithelial cells in endometriosis," Biology of Reproduction 99(5), 968-981, (31 May 2018). https://doi.org/10.1093/biolre/ioy128
Received: 2 December 2017; Accepted: 30 May 2018; Published: 31 May 2018
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KEYWORDS
autophagy
endometriosis
epithelial–mesenchymal transition
HIF-1α
hypoxia
invasion
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