NME1抑制在子宫内膜异位环境中通过Akt和MAPK/Erk1/2信号通路促进子宫内膜基质细胞的生长、粘附和植入

Abstract

STUDY QUESTIONIs 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?SUMMARY ANSWERNME1 suppression induces ESC dysfunction in the endometriotic milieu.WHAT IS KNOWN ALREADYNME1 is a wide-spectrum tumor metastasis suppressor gene that plays an important role in suppressing the invasion and metastasis of tumor cells.STUDY DESIGN, SIZE, DURATIONAn in vitro investigation of the effect of NME1 on the proliferation, adhesion and invasion of eutopic ESCs from patients with endometriosis.PARTICIPANTS/MATERIALS, SETTING, METHODSPrimary 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.MAIN RESULTS AND THE ROLE OF CHANCEExpression 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.LIMITATIONS, REASONS FOR CAUTIONFurther studies are needed to examine the regulatory mechanism of estrogen on NME1 expression of ESCs.WIDER IMPLICATIONS OF THE FINDINGSAbnormally 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.