PDCD4 suppresses proliferation, migration, and invasion of endometrial cells by inhibiting autophagy and NF-κB/MMP2/MMP9 signal pathway

• Published in: Biology of reproduction Vol. 99; no. 2; pp. 360 - 372
• Main Authors: Li, Yue, Wang, Xiaoyan, Wang, Xishuang, Wan, Lu, Liu, Yanping, Shi, Yongyu, Zhang, Lining, Fang, Zhenghui, Wei, Zengtao
• Format: Journal Article
• Language: English
• Published: United States Society for the Study of Reproduction 01.08.2018; Oxford University Press
• Subjects: Autophagy; Cell death; Endometriosis; FEMALE REPRODUCTIVE TRACT; invasion; migration; programmed cell death 4 (PDCD4); proliferation; Reproductive health; endometriosis; migration; proliferation; invasion; programmed cell death 4 (PDCD4)
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1093/biolre/ioy052

Endometriosis (EM) is a kind of estrogen-dependent disease in reproductive-age women. Ovarian EM is the most common type. Although EM is a benign disease, it shares many similar features with cancers. Programmed cell death 4 (PDCD4), a newly identified tumor suppressor, plays an important role in inhibiting tumorigenesis and tumor progression at the transcriptional and translational levels. To explore the roles of PDCD4 in EM,we detected the expression of PDCD4 in control endometrium and eutopic/ectopic endometrium of ovarian EM patients, and analyzed the effects of PDCD4 on the biological behaviors of endometrial cell lines and primary endometrial cells. The results demonstrated that PDCD4 was downregulated in eutopic and ectopic endometrium of EM patients compared with control endometrium. PDCD4 effectively inhibited the proliferation and colony-forming ability of endometrial cells maybe by inhibiting cell autophagy. In addition, PDCD4 also suppressed the migration and invasion ability of endometrial cells, the mechanism may be related to NF-κB/MMP2/MMP9 signal pathway. Taken together, these results suggest that PDCD4 could be involved in the pathogenesis of EM, and provide a novel approach to target the aberrant PDCD4 expression in EM. Summary Sentence PDCD4 suppresses proliferation, migration, and invasion of endometrial cells by the inhibition of autophagy and inactivation of NF-κB/MMP2/MMP9 signal pathway.