title: Hypoxia-inducible factor-1α promotes endometrial stromal cells migration and invasion by upregulating autophagy in endometriosis.
abstract: Endometriosis is a benign gynecological disease that shares some characteristics with malignancy like migration and invasion. It has been reported that both hypoxia-inducible factor-1α (HIF-1α) and autophagy were upregulated in ectopic endometrium of patients with ovarian endometriosis. However, the crosstalk between HIF-1α and autophagy in the pathogenesis of endometriosis remains to be clarified. Accordingly, we investigated whether autophagy was regulated by HIF-1α, as well as whether the effect of HIF-1α on cell migration and invasion is mediated through autophagy upregulation. Here, we found that ectopic endometrium from patients with endometriosis highly expressed HIF-1α and autophagy-related protein LC3. In cultured human endometrial stromal cells (HESCs), autophagy was induced by hypoxia in a time-dependent manner and autophagy activation was dependent on HIF-1α. In addition, migration and invasion ability of HESCs were enhanced by hypoxia treatment, whereas knockdown of HIF-1α attenuated this effect. Furthermore, inhibiting autophagy with specific inhibitors and Beclin1 siRNA attenuated hypoxia triggered migration and invasion of HESCs. Taken together, these results suggest that HIF-1α promotes HESCs invasion and metastasis by upregulating autophagy. Thus, autophagy may be involved in the pathogenesis of endometriosis and inhibition of autophagy might be a novel therapeutic approach to the treatment of endometriosis.
authors.affiliation: Department of Obstetrics and GynecologyUnion Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hengwei
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and GynecologyVirginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and GynecologyUnion Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Wenqian
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Department of Obstetrics and GynecologyUnion Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and GynecologyUnion Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Obstetrics and GynecologyUnion Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Obstetrics and GynecologyUnion Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Haitang
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Obstetrics and GynecologyUnion Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Obstetrics and GynecologyUnion Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Liqun94@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000328:Adult; D001343:Autophagy; D002448:Cell Adhesion; D015687:Cell Hypoxia; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004715:Endometriosis / Q000378:metabolism / Q000473:pathology*; D004717:Endometrium / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins