title: NME1 suppression promotes growth, adhesion and implantation of endometrial stromal cells via Akt and MAPK/Erk1/2 signal pathways in the endometriotic milieu.
abstract: OBJECTIVE
  Is Nometastatic gene 23-H1 (NME1, also known as nm23-H1) involved in regulating the biological behavior of endometrial stromal cells (ESCs), and does it participate in the pathogenesis of endometriosis?
  
  
  CONCLUSIONS
  NME1 suppression induces ESC dysfunction in the endometriotic milieu.
  
  
  BACKGROUND
  NME1 is a wide-spectrum tumor metastasis suppressor gene that plays an important role in suppressing the invasion and metastasis of tumor cells.
  
  
  METHODS
  An in vitro investigation of the effect of NME1 on the proliferation, adhesion and invasion of eutopic ESCs from patients with endometriosis.
  
  
  METHODS
  Primary ESCs were prepared from 12 samples of ectopic endometrial tissue (6 peritoneal and 6 ovarian lesions), 18 samples of eutopic endometrial tissues (16 from women with ovarian and 2 from women with pelvic endometriomas) and 12 samples of normal endometrial tissue from women without endometriosis, after the tissues had been analyzed histologically. The growth, invasiveness and adhesion of ESCs were studied by the 5-bromo-2'-deoxyuridine cell proliferation assay and by the Matrigel invasion and adhesion assay. Additionally, the effects of NME1 on the activation or expression of related regulatory proteins were investigated by in-cell Western and flow cytometry assays.
  
  
  RESULTS
  Expression of NME1 in ESCs derived from eutopic or ectopic endometrium from women with endometriosis is lower than in ESCs from women without endometriosis. Estrogen could down-regulate NME1 expression in ESCs. Silencing NME1 in ESCs promoted the expression of proliferating cell nuclear antigen (PCNA), the anti-apoptotic molecule, survivin, and the adhesion-related molecules, integrin β1 and integrin ανβ3. Silencing NME1 also stimulated ESC proliferation, adhesion and invasion but these effects were inhibited by MAPK/Erk and/or Akt blockers.
  
  
  CONCLUSIONS
  Further studies are needed to examine the regulatory mechanism of estrogen on NME1 expression of ESCs.
  
  
  CONCLUSIONS
  Abnormally low expression of NME1 in ESCs may be involved in the pathogenesis of endometriosis by up-regulating growth, adhesion and invasion of ESCs via activating the Akt and MAPK/Erk1/2 signal pathways.
  
  
  BACKGROUND
  This work was supported by National Natural Science Foundation of China (NSFC) (31270969, 31101064 and 81270677) and Program for ZhouXue of Fudan University. None of the authors has any conflict of interest to declare.
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, No. 413, Zhaozhou Road, Shanghai 200011, China.
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Shao
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Meng
authors.forename: Jie
authors.initials: J
authors.lastname: Mei
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Kai-Kai
authors.initials: KK
authors.lastname: Chang
authors.forename: Xiao-Qiu
authors.initials: XQ
authors.lastname: Wang
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Zhu
authors.forename: Da-Jin
authors.initials: DJ
authors.lastname: Li
mesh_terms: D002448:Cell Adhesion; D049109:Cell Proliferation; D015536:Down-Regulation / Q000187:drug effects; D004715:Endometriosis / Q000378:metabolism / Q000473:pathology*; D004717:Endometrium / Q000378:metabolism / Q000473:pathology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D054778:NM23 Nucleoside Diphosphate Kinases / Q000378:metabolism / Q000502:physiology*; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D004967:Estrogens; D051034:Inhibitor of Apoptosis Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D018809:Proliferating Cell Nuclear Antigen; D000077022:Survivin; D051058:Oncogene Protein v-akt; C517938:NME1 protein, human
keywords: NME1; adhesion; endometriosis; invasion; proliferation