Skip to main content
Top
Published in: Reproductive Biology and Endocrinology 1/2018

Open Access 01-12-2018 | Research

Melatonin inhibits 17β-estradiol-induced migration, invasion and epithelial-mesenchymal transition in normal and endometriotic endometrial epithelial cells

Authors: Shasha Qi, Lei Yan, Zhao Liu, Yu-lan Mu, Mingjiang Li, Xingbo Zhao, Zi-Jiang Chen, Hui Zhang

Published in: Reproductive Biology and Endocrinology | Issue 1/2018

Login to get access

Abstract

Background

Melatonin is a potential therapeutic agent for endometriosis, but its molecular mechanism is unclear. Here, we investigated the effect of melatonin on the epithelial-mesenchymal transition (EMT) in endometriotic endometrial epithelial cells and explored the pathway that might be involved.

Methods

This hospital-based study included 60 women of reproductive age using the endometrium for immunohistochemistry, 6 women of reproductive age undergoing bilateral tubal ligation and 6 patients with endometriosis for isolation of endometrial epithelial cells or subsequent analysis, respectively. We examined the expression of Notch1/Numb signaling and EMT markers by immunohistochemistry analysis and western blot analysis, the invasion and migration of endometrial epithelial cells by transwell assays, and the cell proliferation by CCK8 assays.

Results

Compared with normal endometrium, the endometriotic eutopic endometrium showed increased expression of Notch1, Slug, Snail, and N-cadherin, and decreased expression of E-cadherin and Numb. Melatonin or Notch inhibition by specific inhibitor blocked 17β-estradiol-induced cell proliferation, invasion, migration and EMT-related markers in both normal and endometriotic epithelial cells.

Conclusions

Our data suggest that aberrant expression of Notch1/Numb signaling and the EMT is present in endometriotic endometrium. Melatonin may block 17β-estradiol-induced migration, invasion and EMT in normal and endometriotic epithelial cells by upregulating Numb expression and decreasing the activity of the Notch signaling pathway.
Literature
2.
go back to reference Simoens S, Dunselman G, Dirksen C, Hummelshoj L, Bokor A, Brandes I, et al. The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres. Hum Reprod. 2012;27:1292–9.CrossRefPubMed Simoens S, Dunselman G, Dirksen C, Hummelshoj L, Bokor A, Brandes I, et al. The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres. Hum Reprod. 2012;27:1292–9.CrossRefPubMed
4.
go back to reference Matsuzaki S, Darcha C. Epithelial to mesenchymal transition-like and mesenchymal to epithelial transition-like processes might be involved in the pathogenesis of pelvic endometriosis. Hum Reprod. 2012;27:712–21.CrossRefPubMed Matsuzaki S, Darcha C. Epithelial to mesenchymal transition-like and mesenchymal to epithelial transition-like processes might be involved in the pathogenesis of pelvic endometriosis. Hum Reprod. 2012;27:712–21.CrossRefPubMed
5.
6.
go back to reference Liu Z, Qi S, Zhao X, Li M, Ding S, Lu J, et al. Metformin inhibits 17beta-estradiol-induced epithelial-to-mesenchymal transition via betaKlotho-related ERK1/2 signaling and AMPKalpha signaling in endometrial adenocarcinoma cells. Oncotarget. 2016;7:21315–31.PubMedPubMedCentral Liu Z, Qi S, Zhao X, Li M, Ding S, Lu J, et al. Metformin inhibits 17beta-estradiol-induced epithelial-to-mesenchymal transition via betaKlotho-related ERK1/2 signaling and AMPKalpha signaling in endometrial adenocarcinoma cells. Oncotarget. 2016;7:21315–31.PubMedPubMedCentral
7.
go back to reference Dong C, Wu Y, Yao J, Wang Y, Yu Y, Rychahou PG, et al. G9a interacts with snail and is critical for snail-mediated E-cadherin repression in human breast cancer. J Clin Invest. 2012;122:1469–86.CrossRefPubMedPubMedCentral Dong C, Wu Y, Yao J, Wang Y, Yu Y, Rychahou PG, et al. G9a interacts with snail and is critical for snail-mediated E-cadherin repression in human breast cancer. J Clin Invest. 2012;122:1469–86.CrossRefPubMedPubMedCentral
8.
go back to reference Qi S, Zhao X, Li M, Zhang X, Lu Z, Yang C, et al. Aberrant expression of Notch1/numb/snail signaling, an epithelial mesenchymal transition related pathway, in adenomyosis. Reprod Biol Endocrinol. 2015;13:96.CrossRefPubMedPubMedCentral Qi S, Zhao X, Li M, Zhang X, Lu Z, Yang C, et al. Aberrant expression of Notch1/numb/snail signaling, an epithelial mesenchymal transition related pathway, in adenomyosis. Reprod Biol Endocrinol. 2015;13:96.CrossRefPubMedPubMedCentral
9.
go back to reference Reiter RJ. Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocr Rev. 1991;12:151–80.CrossRefPubMed Reiter RJ. Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocr Rev. 1991;12:151–80.CrossRefPubMed
10.
go back to reference Cetinkaya N, Attar R, Yildirim G, Ficicioglu C, Ozkan F, Yilmaz B, et al. The effects of different doses of melatonin treatment on endometrial implants in an oophorectomized rat endometriosis model. Arch Gynecol Obstet. 2015;291:591–8.CrossRefPubMed Cetinkaya N, Attar R, Yildirim G, Ficicioglu C, Ozkan F, Yilmaz B, et al. The effects of different doses of melatonin treatment on endometrial implants in an oophorectomized rat endometriosis model. Arch Gynecol Obstet. 2015;291:591–8.CrossRefPubMed
11.
go back to reference Guney M, Oral B, Karahan N, Mungan T. Regression of endometrial explants in a rat model of endometriosis treated with melatonin. Fertil Steril. 2008;89:934–42.CrossRefPubMed Guney M, Oral B, Karahan N, Mungan T. Regression of endometrial explants in a rat model of endometriosis treated with melatonin. Fertil Steril. 2008;89:934–42.CrossRefPubMed
12.
go back to reference Koc O, Gunduz B, Topcuoglu A, Bugdayci G, Yilmaz F, Duran B. Effects of pinealectomy and melatonin supplementation on endometrial explants in a rat model. Eur J Obstet Gynecol Reprod Biol. 2010;153:72–6.CrossRefPubMed Koc O, Gunduz B, Topcuoglu A, Bugdayci G, Yilmaz F, Duran B. Effects of pinealectomy and melatonin supplementation on endometrial explants in a rat model. Eur J Obstet Gynecol Reprod Biol. 2010;153:72–6.CrossRefPubMed
13.
go back to reference Kocadal NC, Attar R, Yildirim G, Ficicioglu C, Ozkan F, Yilmaz B, et al. Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model. J Turk Ger Gynecol Assoc. 2013;14:81–6.CrossRefPubMedPubMedCentral Kocadal NC, Attar R, Yildirim G, Ficicioglu C, Ozkan F, Yilmaz B, et al. Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model. J Turk Ger Gynecol Assoc. 2013;14:81–6.CrossRefPubMedPubMedCentral
14.
go back to reference Yesildaglar N, Yildirim G, Yildirim OK, Attar R, Ozkan F, Akkaya H, et al. The effects of melatonin on endometriotic lesions induced by implanting human endometriotic cells in the first SCID-mouse endometriosis-model developed in Turkey. Clin Exp Obstet Gynecol. 2016;43:25–30.PubMed Yesildaglar N, Yildirim G, Yildirim OK, Attar R, Ozkan F, Akkaya H, et al. The effects of melatonin on endometriotic lesions induced by implanting human endometriotic cells in the first SCID-mouse endometriosis-model developed in Turkey. Clin Exp Obstet Gynecol. 2016;43:25–30.PubMed
15.
go back to reference Yildirim G, Attar R, Ficicioglu C, Karateke A, Ozkan F, Kilic E, et al. The combination of letrozole and melatonin causes regression in size not histopathological scores on endometriosis in an experimental rat model. J Turk Ger Gynecol Assoc. 2009;10:199–204.PubMedPubMedCentral Yildirim G, Attar R, Ficicioglu C, Karateke A, Ozkan F, Kilic E, et al. The combination of letrozole and melatonin causes regression in size not histopathological scores on endometriosis in an experimental rat model. J Turk Ger Gynecol Assoc. 2009;10:199–204.PubMedPubMedCentral
16.
go back to reference Yildirim G, Attar R, Ozkan F, Kumbak B, Ficicioglu C, Yesildaglar N. The effects of letrozole and melatonin on surgically induced endometriosis in a rat model: a preliminary study. Fertil Steril. 2010;93:1787–92.CrossRefPubMed Yildirim G, Attar R, Ozkan F, Kumbak B, Ficicioglu C, Yesildaglar N. The effects of letrozole and melatonin on surgically induced endometriosis in a rat model: a preliminary study. Fertil Steril. 2010;93:1787–92.CrossRefPubMed
17.
go back to reference Shi S, Zhang Y, Wen W, Zhao Y, Sun L. Molecular mechanisms of melatonin in the reversal of LPS-induced EMT in peritoneal mesothelial cells. Mol Med Rep. 2016;14:4342–8.CrossRefPubMed Shi S, Zhang Y, Wen W, Zhao Y, Sun L. Molecular mechanisms of melatonin in the reversal of LPS-induced EMT in peritoneal mesothelial cells. Mol Med Rep. 2016;14:4342–8.CrossRefPubMed
18.
go back to reference Yu N, Sun YT, Su XM, He M, Dai B, Kang J. Melatonin attenuates TGFbeta1-induced epithelial-mesenchymal transition in lung alveolar epithelial cells. Mol Med Rep. 2016;14:5567–72.CrossRefPubMed Yu N, Sun YT, Su XM, He M, Dai B, Kang J. Melatonin attenuates TGFbeta1-induced epithelial-mesenchymal transition in lung alveolar epithelial cells. Mol Med Rep. 2016;14:5567–72.CrossRefPubMed
19.
go back to reference Zhao H, Wu QQ, Cao LF, Qing HY, Zhang C, Chen YH, et al. Melatonin inhibits endoplasmic reticulum stress and epithelial-mesenchymal transition during bleomycin-induced pulmonary fibrosis in mice. PLoS One. 2014;9:e97266.CrossRefPubMedPubMedCentral Zhao H, Wu QQ, Cao LF, Qing HY, Zhang C, Chen YH, et al. Melatonin inhibits endoplasmic reticulum stress and epithelial-mesenchymal transition during bleomycin-induced pulmonary fibrosis in mice. PLoS One. 2014;9:e97266.CrossRefPubMedPubMedCentral
20.
go back to reference Zhang H, Li M, Zheng X, Sun Y, Wen Z, Zhao X. Endometriotic stromal cells lose the ability to regulate cell-survival signaling in endometrial epithelial cells in vitro. Mol Hum Reprod. 2009;15:653–63.CrossRefPubMed Zhang H, Li M, Zheng X, Sun Y, Wen Z, Zhao X. Endometriotic stromal cells lose the ability to regulate cell-survival signaling in endometrial epithelial cells in vitro. Mol Hum Reprod. 2009;15:653–63.CrossRefPubMed
21.
go back to reference Zhang H, Li M, Wang F, Liu S, Li J, Wen Z, et al. Endometriotic epithelial cells induce MMPs expression in endometrial stromal cells via an NFkappaB-dependent pathway. Gynecol Endocrinol. 2010;26:456–67.CrossRefPubMed Zhang H, Li M, Wang F, Liu S, Li J, Wen Z, et al. Endometriotic epithelial cells induce MMPs expression in endometrial stromal cells via an NFkappaB-dependent pathway. Gynecol Endocrinol. 2010;26:456–67.CrossRefPubMed
22.
go back to reference Wu SM, Lin WY, Shen CC, Pan HC, Keh-Bin W, Chen YC, et al. Melatonin set out to ER stress signaling thwarts epithelial mesenchymal transition and peritoneal dissemination via calpain-mediated C/EBPbeta and NFkappaB cleavage. J Pineal Res. 2016;60:142–54.CrossRefPubMed Wu SM, Lin WY, Shen CC, Pan HC, Keh-Bin W, Chen YC, et al. Melatonin set out to ER stress signaling thwarts epithelial mesenchymal transition and peritoneal dissemination via calpain-mediated C/EBPbeta and NFkappaB cleavage. J Pineal Res. 2016;60:142–54.CrossRefPubMed
23.
go back to reference Prieto-Dominguez N, Ordonez R, Fernandez A, Mendez-Blanco C, Baulies A, Garcia-Ruiz C, et al. Melatonin-induced increase in sensitivity of human hepatocellular carcinoma cells to sorafenib is associated with reactive oxygen species production and mitophagy. J Pineal Res. 2016;61:396–407.CrossRefPubMedPubMedCentral Prieto-Dominguez N, Ordonez R, Fernandez A, Mendez-Blanco C, Baulies A, Garcia-Ruiz C, et al. Melatonin-induced increase in sensitivity of human hepatocellular carcinoma cells to sorafenib is associated with reactive oxygen species production and mitophagy. J Pineal Res. 2016;61:396–407.CrossRefPubMedPubMedCentral
24.
go back to reference Gao W, Sweeney C, Walsh C, Rooney P, McCormick J, Veale DJ, et al. Notch signalling pathways mediate synovial angiogenesis in response to vascular endothelial growth factor and angiopoietin 2. Ann Rheum Dis. 2013;72:1080–8.CrossRefPubMed Gao W, Sweeney C, Walsh C, Rooney P, McCormick J, Veale DJ, et al. Notch signalling pathways mediate synovial angiogenesis in response to vascular endothelial growth factor and angiopoietin 2. Ann Rheum Dis. 2013;72:1080–8.CrossRefPubMed
25.
go back to reference Song BQ, Chi Y, Li X, Du WJ, Han ZB, Tian JJ, et al. Inhibition of notch signaling promotes the Adipogenic differentiation of mesenchymal stem cells through autophagy activation and PTEN-PI3K/AKT/mTOR pathway. Cell Physiol Biochem. 2015;36:1991–2002.CrossRefPubMed Song BQ, Chi Y, Li X, Du WJ, Han ZB, Tian JJ, et al. Inhibition of notch signaling promotes the Adipogenic differentiation of mesenchymal stem cells through autophagy activation and PTEN-PI3K/AKT/mTOR pathway. Cell Physiol Biochem. 2015;36:1991–2002.CrossRefPubMed
26.
go back to reference Ray S, Pollard JW. KLF15 negatively regulates estrogen-induced epithelial cell proliferation by inhibition of DNA replication licensing. Proc Natl Acad Sci U S A. 2012;109:E1334–43.CrossRefPubMedPubMedCentral Ray S, Pollard JW. KLF15 negatively regulates estrogen-induced epithelial cell proliferation by inhibition of DNA replication licensing. Proc Natl Acad Sci U S A. 2012;109:E1334–43.CrossRefPubMedPubMedCentral
27.
go back to reference Meng YG, Han WD, Zhao YL, Huang K, Si YL, Wu ZQ, et al. Induction of the LRP16 gene by estrogen promotes the invasive growth of Ishikawa human endometrial cancer cells through the downregulation of E-cadherin. Cell Res. 2007;17:869–80.CrossRefPubMed Meng YG, Han WD, Zhao YL, Huang K, Si YL, Wu ZQ, et al. Induction of the LRP16 gene by estrogen promotes the invasive growth of Ishikawa human endometrial cancer cells through the downregulation of E-cadherin. Cell Res. 2007;17:869–80.CrossRefPubMed
28.
go back to reference Leyendecker G, Wildt L, Mall G. The pathophysiology of endometriosis and adenomyosis: tissue injury and repair. Arch Gynecol Obstet. 2009;280:529–38.CrossRefPubMedPubMedCentral Leyendecker G, Wildt L, Mall G. The pathophysiology of endometriosis and adenomyosis: tissue injury and repair. Arch Gynecol Obstet. 2009;280:529–38.CrossRefPubMedPubMedCentral
29.
go back to reference Leong KG, Niessen K, Kulic I, Raouf A, Eaves C, Pollet I, et al. Jagged1-mediated notch activation induces epithelial-to-mesenchymal transition through slug-induced repression of E-cadherin. J Exp Med. 2007;204:2935–48.CrossRefPubMedPubMedCentral Leong KG, Niessen K, Kulic I, Raouf A, Eaves C, Pollet I, et al. Jagged1-mediated notch activation induces epithelial-to-mesenchymal transition through slug-induced repression of E-cadherin. J Exp Med. 2007;204:2935–48.CrossRefPubMedPubMedCentral
30.
go back to reference Matsuno Y, Coelho AL, Jarai G, Westwick J, Hogaboam CM. Notch signaling mediates TGF-beta1-induced epithelial-mesenchymal transition through the induction of Snai1. Int J Biochem Cell Biol. 2012;44:776–89.CrossRefPubMed Matsuno Y, Coelho AL, Jarai G, Westwick J, Hogaboam CM. Notch signaling mediates TGF-beta1-induced epithelial-mesenchymal transition through the induction of Snai1. Int J Biochem Cell Biol. 2012;44:776–89.CrossRefPubMed
31.
go back to reference McGill MA, McGlade CJ. Mammalian numb proteins promote Notch1 receptor ubiquitination and degradation of the Notch1 intracellular domain. J Biol Chem. 2003;278:23196–203.CrossRefPubMed McGill MA, McGlade CJ. Mammalian numb proteins promote Notch1 receptor ubiquitination and degradation of the Notch1 intracellular domain. J Biol Chem. 2003;278:23196–203.CrossRefPubMed
32.
go back to reference Xiong Y, Liu Y, Xiong W, Zhang L, Liu H, Du Y, et al. Hypoxia-inducible factor 1alpha-induced epithelial-mesenchymal transition of endometrial epithelial cells may contribute to the development of endometriosis. Hum Reprod. 2016;31:1327–38.CrossRefPubMed Xiong Y, Liu Y, Xiong W, Zhang L, Liu H, Du Y, et al. Hypoxia-inducible factor 1alpha-induced epithelial-mesenchymal transition of endometrial epithelial cells may contribute to the development of endometriosis. Hum Reprod. 2016;31:1327–38.CrossRefPubMed
33.
go back to reference Zheng QM, Lu JJ, Zhao J, Wei X, Wang L, Liu PS. Periostin facilitates the epithelial-mesenchymal transition of endometrial epithelial cells through ILK-Akt signaling pathway. Biomed Res Int. 2016;2016:9842619.PubMedPubMedCentral Zheng QM, Lu JJ, Zhao J, Wei X, Wang L, Liu PS. Periostin facilitates the epithelial-mesenchymal transition of endometrial epithelial cells through ILK-Akt signaling pathway. Biomed Res Int. 2016;2016:9842619.PubMedPubMedCentral
34.
go back to reference Yang YM, Yang WX. Epithelial-to-mesenchymal transition in the development of endometriosis. Oncotarget. 2017;8:41679–89.PubMedPubMedCentral Yang YM, Yang WX. Epithelial-to-mesenchymal transition in the development of endometriosis. Oncotarget. 2017;8:41679–89.PubMedPubMedCentral
35.
go back to reference Bulun SE, Zeitoun KM, Takayama K, Sasano H. Estrogen biosynthesis in endometriosis: molecular basis and clinical relevance. J Mol Endocrinol. 2000;25:35–42.CrossRefPubMed Bulun SE, Zeitoun KM, Takayama K, Sasano H. Estrogen biosynthesis in endometriosis: molecular basis and clinical relevance. J Mol Endocrinol. 2000;25:35–42.CrossRefPubMed
36.
go back to reference Ye Y, Xiao Y, Wang W, Yearsley K, Gao JX, Shetuni B, et al. ERalpha signaling through slug regulates E-cadherin and EMT. Oncogene. 2010;29:1451–62.CrossRefPubMed Ye Y, Xiao Y, Wang W, Yearsley K, Gao JX, Shetuni B, et al. ERalpha signaling through slug regulates E-cadherin and EMT. Oncogene. 2010;29:1451–62.CrossRefPubMed
37.
go back to reference Chimge NO, Baniwal SK, Little GH, Chen YB, Kahn M, Tripathy D, et al. Regulation of breast cancer metastasis by Runx2 and estrogen signaling: the role of SNAI2. Breast Cancer Res. 2011;13:R127.CrossRefPubMedPubMedCentral Chimge NO, Baniwal SK, Little GH, Chen YB, Kahn M, Tripathy D, et al. Regulation of breast cancer metastasis by Runx2 and estrogen signaling: the role of SNAI2. Breast Cancer Res. 2011;13:R127.CrossRefPubMedPubMedCentral
38.
go back to reference Jeon SY, Hwang KA, Choi KC. Effect of steroid hormones, estrogen and progesterone, on epithelial mesenchymal transition in ovarian cancer development. J Steroid Biochem Mol Biol. 2016;158:1–8.CrossRefPubMed Jeon SY, Hwang KA, Choi KC. Effect of steroid hormones, estrogen and progesterone, on epithelial mesenchymal transition in ovarian cancer development. J Steroid Biochem Mol Biol. 2016;158:1–8.CrossRefPubMed
39.
go back to reference Shao R, Shi J, Liu H, Shi X, Du X, Klocker H, et al. Epithelial-to-mesenchymal transition and estrogen receptor alpha mediated epithelial dedifferentiation mark the development of benign prostatic hyperplasia. Prostate. 2014;74:970–82.CrossRefPubMed Shao R, Shi J, Liu H, Shi X, Du X, Klocker H, et al. Epithelial-to-mesenchymal transition and estrogen receptor alpha mediated epithelial dedifferentiation mark the development of benign prostatic hyperplasia. Prostate. 2014;74:970–82.CrossRefPubMed
40.
go back to reference Paul S, Bhattacharya P, Das Mahapatra P, Swarnakar S. Melatonin protects against endometriosis via regulation of matrix metalloproteinase-3 and an apoptotic pathway. J Pineal Res. 2010;49:156–68.PubMed Paul S, Bhattacharya P, Das Mahapatra P, Swarnakar S. Melatonin protects against endometriosis via regulation of matrix metalloproteinase-3 and an apoptotic pathway. J Pineal Res. 2010;49:156–68.PubMed
41.
go back to reference Paul S, Sharma AV, Mahapatra PD, Bhattacharya P, Reiter RJ, Swarnakar S. Role of melatonin in regulating matrix metalloproteinase-9 via tissue inhibitors of metalloproteinase-1 during protection against endometriosis. J Pineal Res. 2008;44:439–49.CrossRefPubMed Paul S, Sharma AV, Mahapatra PD, Bhattacharya P, Reiter RJ, Swarnakar S. Role of melatonin in regulating matrix metalloproteinase-9 via tissue inhibitors of metalloproteinase-1 during protection against endometriosis. J Pineal Res. 2008;44:439–49.CrossRefPubMed
42.
go back to reference Schwertner A, Conceicao Dos Santos CC, Costa GD, Deitos A, de Souza A, de Souza IC, et al. Efficacy of melatonin in the treatment of endometriosis: a phase II, randomized, double-blind, placebo-controlled trial. Pain. 2013;154:874–81.CrossRefPubMed Schwertner A, Conceicao Dos Santos CC, Costa GD, Deitos A, de Souza A, de Souza IC, et al. Efficacy of melatonin in the treatment of endometriosis: a phase II, randomized, double-blind, placebo-controlled trial. Pain. 2013;154:874–81.CrossRefPubMed
43.
go back to reference Bondi CD, Alonso-Gonzalez C, Clafshenkel WP, Kotlarczyk MP, Dodda BR, Sanchez-Barcelo E, et al. The effect of estradiol, progesterone, and melatonin on estrous cycling and ovarian aromatase expression in intact female mice. Eur J Obstet Gynecol Reprod Biol. 2014;174:80–5.CrossRefPubMed Bondi CD, Alonso-Gonzalez C, Clafshenkel WP, Kotlarczyk MP, Dodda BR, Sanchez-Barcelo E, et al. The effect of estradiol, progesterone, and melatonin on estrous cycling and ovarian aromatase expression in intact female mice. Eur J Obstet Gynecol Reprod Biol. 2014;174:80–5.CrossRefPubMed
44.
go back to reference Berstein L, Tsyrlina E, Poroshina T, Bychkova N, Kalinina N, Gamajunova V, et al. Switching (overtargeting) of estrogen effects and its potential role in hormonal carcinogenesis. Neoplasma. 2002;49:21–5.PubMed Berstein L, Tsyrlina E, Poroshina T, Bychkova N, Kalinina N, Gamajunova V, et al. Switching (overtargeting) of estrogen effects and its potential role in hormonal carcinogenesis. Neoplasma. 2002;49:21–5.PubMed
45.
go back to reference Ciortea R, Costin N, Braicu I, Haragas D, Hudacsko A, Bondor C, et al. Effect of melatonin on intra-abdominal fat in correlation with endometrial proliferation in ovariectomized rats. Anticancer Res. 2011;31:2637–43.PubMed Ciortea R, Costin N, Braicu I, Haragas D, Hudacsko A, Bondor C, et al. Effect of melatonin on intra-abdominal fat in correlation with endometrial proliferation in ovariectomized rats. Anticancer Res. 2011;31:2637–43.PubMed
46.
go back to reference Dair EL, Simoes RS, Simoes MJ, Romeu LR, Oliveira-Filho RM, Haidar MA, et al. Effects of melatonin on the endometrial morphology and embryo implantation in rats. Fertil Steril. 2008;89:1299–305.CrossRefPubMed Dair EL, Simoes RS, Simoes MJ, Romeu LR, Oliveira-Filho RM, Haidar MA, et al. Effects of melatonin on the endometrial morphology and embryo implantation in rats. Fertil Steril. 2008;89:1299–305.CrossRefPubMed
47.
go back to reference Zhang J, Shao X, Sun H, Liu K, Ding Z, Chen J, et al. NUMB negatively regulates the epithelial-mesenchymal transition of triple-negative breast cancer by antagonizing notch signaling. Oncotarget. 2016;7:61036–53.PubMedPubMedCentral Zhang J, Shao X, Sun H, Liu K, Ding Z, Chen J, et al. NUMB negatively regulates the epithelial-mesenchymal transition of triple-negative breast cancer by antagonizing notch signaling. Oncotarget. 2016;7:61036–53.PubMedPubMedCentral
48.
go back to reference Bocci F, Jolly MK, Tripathi SC, Aguilar M, Hanash SM, Levine H, et al. Numb prevents a complete epithelial-mesenchymal transition by modulating notch signalling. J R Soc Interface. 2017;14 Bocci F, Jolly MK, Tripathi SC, Aguilar M, Hanash SM, Levine H, et al. Numb prevents a complete epithelial-mesenchymal transition by modulating notch signalling. J R Soc Interface. 2017;14
Metadata
Title
Melatonin inhibits 17β-estradiol-induced migration, invasion and epithelial-mesenchymal transition in normal and endometriotic endometrial epithelial cells
Authors
Shasha Qi
Lei Yan
Zhao Liu
Yu-lan Mu
Mingjiang Li
Xingbo Zhao
Zi-Jiang Chen
Hui Zhang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2018
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-018-0375-5

Other articles of this Issue 1/2018

Reproductive Biology and Endocrinology 1/2018 Go to the issue