Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2015

Open Access 01-12-2015 | Research

Aberrant expression of Notch1/numb/snail signaling, an epithelial mesenchymal transition related pathway, in adenomyosis

Authors: Shasha Qi, Xingbo Zhao, Mingjiang Li, Xiaohui Zhang, Zhenzhen Lu, Chunrun Yang, Chunhua Zhang, Hui Zhang, Na Zhang

Published in: Reproductive Biology and Endocrinology | Issue 1/2015

Login to get access

Abstract

Background

Epithelial mesenchymal transition (EMT) is involved in the pathogenesis of adenomyosis, and Notch signaling is crucial to EMT. The objective of this study was to explore Notch1/Numb/Snail signaling in adenomyosis.

Methods

The expression levels of the members of the Notch1/Numb/Snail signaling cascade in normal endometria (proliferative phase: n = 15; secretory phase: n = 15; postmenopausal phase: n = 15) and adenomyotic endometria (proliferative phase: n = 15; secretory phase: n = 15) were determined by immunohistochemistry analysis.

Results

We found that the expressions of Notch1 and the EMT-related proteins N-cadherin, Snail and Slug were upregulated in the ectopic endometrium of adenomyosis compared with normal endometrium. Numb, a negative regulator of Notch signaling, was significantly decreased in adenomyosis. In addition, reduced immunoexpression of E-cadherin was observed in adenomyosis.

Conclusions

We conclude that Notch1/Numb/Snail signaling plays an important role in the pathogenesis and development of adenomyosis.
Literature
1.
Guo Q, Zhang H, Zhao X, Fu Y, Zhang J, Li M. Loss of expressions of Dusp6, Sprouty4, and Sef, negative regulators of FGF2/ERK1/2 signaling, in the endometrium of women with adenomyosis. Int J Gynecol Pathol. 2014;33:288–97.CrossRefPubMed
2.
Di Donato N, Seracchioli R. How to evaluate adenomyosis in patients affected by endometriosis? Minim Invasive Surg. 2014;2014:507230.PubMedCentralPubMed
3.
Marie-Egyptienne DT, Lohse I, Hill RP. Cancer stem cells, the epithelial to mesenchymal transition (EMT) and radioresistance: potential role of hypoxia. Cancer Lett. 2013;341:63–72.CrossRefPubMed
4.
Voulgari A, Pintzas A. Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta. 2009;1796:75–90.PubMed
5.
Iwatsuki M, Mimori K, Yokobori T, Ishi H, Beppu T, Nakamori S, et al. Epithelial-mesenchymal transition in cancer development and its clinical significance. Cancer Sci. 2010;101:293–9.CrossRefPubMed
6.
7.
8.
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
9.
10.
Chen YJ, Li HY, Huang CH, Twu NF, Yen MS, Wang PH, et al. Oestrogen-induced epithelial-mesenchymal transition of endometrial epithelial cells contributes to the development of adenomyosis. J Pathol. 2010;222:261–70.CrossRefPubMed
11.
Wang Z, Li Y, Kong D, Sarkar FH. The role of notch signaling pathway in Epithelial-Mesenchymal Transition (EMT) during development and tumor aggressiveness. Curr Drug Targets. 2010;11:745–51.PubMedCentralCrossRefPubMed
12.
13.
Chan YM, Jan YN. Roles for proteolysis and trafficking in Notch maturation and signal transduction. Cell. 1998;94:423–6.CrossRefPubMed
14.
Cano A, Perez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, Del Barrio MG, et al. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2000;2:76–83.CrossRefPubMed
15.
Bolos V, Peinado H, Perez-Moreno MA, Fraga MF, Esteller M, Cano A. The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors. J Cell Sci. 2003;116:499–511.CrossRefPubMed
16.
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
17.
Jiang X, Xing H, Kim TM, Jung Y, Huang W, Yang HW, et al. Numb regulates glioma stem cell fate and growth by altering epidermal growth factor receptor and Skp1-Cullin-F-box ubiquitin ligase activity. Stem Cells. 2012;30:1313–26.PubMedCentralCrossRefPubMed
18.
Ito T, Kwon HY, Zimdahl B, Congdon KL, Blum J, Lento WE, et al. Regulation of myeloid leukaemia by the cell-fate determinant Musashi. Nature. 2010;466:765–8.PubMedCentralCrossRefPubMed
19.
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
20.
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.PubMedCentralCrossRefPubMed
21.
Bao B, Wang Z, Ali S, Kong D, Li Y, Ahmad A, et al. Notch-1 induces epithelial-mesenchymal transition consistent with cancer stem cell phenotype in pancreatic cancer cells. Cancer Lett. 2011;307:26–36.PubMedCentralCrossRefPubMed
22.
Xie M, Zhang L, He CS, Xu F, Liu JL, Hu ZH. Activation of Notch-1 enhances epithelial-mesenchymal transition in gefitinib-acquired resistant lung cancer cells. J Cell Biochem. 2012;113:1501–13.PubMed
23.
Sharma A, Paranjape AN, Rangarajan A, Dighe RR. A monoclonal antibody against human Notch1 ligand-binding domain depletes subpopulation of putative breast cancer stem-like cells. Mol Cancer Ther. 2012;11:77–86.CrossRefPubMed
24.
Chen J, Imanaka N, Chen J, Griffin JD. Hypoxia potentiates Notch signaling in breast cancer leading to decreased E-cadherin expression and increased cell migration and invasion. Br J Cancer. 2010;102:351–60.PubMedCentralCrossRefPubMed
25.
Wang XQ, Zhang W, Lui EL, Zhu Y, Lu P, Yu X, et al. Notch1-Snail1-E-cadherin pathway in metastatic hepatocellular carcinoma. Int J Cancer. 2012;131:E163–72.CrossRefPubMed
26.
Leyendecker G, Wildt L, Mall G. The pathophysiology of endometriosis and adenomyosis: tissue injury and repair. Arch Gynecol Obstet. 2009;280:529–38.PubMedCentralCrossRefPubMed
27.
28.
Chang AC, Garside VC, Fournier M, Smrz J, Vrljicak P, Umlandt P, et al. A Notch-dependent transcriptional hierarchy promotes mesenchymal transdifferentiation in the cardiac cushion. Dev Dyn. 2014;243:894–905.CrossRefPubMed
29.
30.
Wu K, Chen K, Wang C, Jiao X, Wang L, Zhou J, et al. Cell fate factor DACH1 represses YB-1-mediated oncogenic transcription and translation. Cancer Res. 2014;74:829–39.PubMedCentralCrossRefPubMed
31.
Mikhailik A, Mazella J, Liang S, Tseng L. Notch ligand-dependent gene expression in human endometrial stromal cells. Biochem Biophys Res Commun. 2009;388:479–82.CrossRefPubMed
32.
Mori M, Miyamoto T, Ohno S, Miyake Y, Sakaguchi T, Ohno E. Diagnostic utility of notch-1 immunocytochemistry in endometrial cytology. Acta Cytol. 2012;56:166–70.CrossRefPubMed
33.
Cobellis L, Caprio F, Trabucco E, Mastrogiacomo A, Coppola G, Manente L, et al. The pattern of expression of Notch protein members in normal and pathological endometrium. J Anat. 2008;213:464–72.PubMedCentralCrossRefPubMed
34.
Afshar Y, Jeong JW, Roqueiro D, Demayo F, Lydon J, Radtke F, et al. Notch1 mediates uterine stromal differentiation and is critical for complete decidualization in the mouse. FASEB J. 2012;26:282–94.PubMedCentralCrossRefPubMed
35.
Afshar Y, Miele L, Fazleabas AT. Notch1 is regulated by chorionic gonadotropin and progesterone in endometrial stromal cells and modulates decidualization in primates. Endocrinology. 2012;153:2884–96.PubMedCentralCrossRefPubMed
36.
Mitsuhashi Y, Horiuchi A, Miyamoto T, Kashima H, Suzuki A, Shiozawa T. Prognostic significance of Notch signalling molecules and their involvement in the invasiveness of endometrial carcinoma cells. Histopathology. 2012;60:826–37.CrossRefPubMed
37.
Mori M, Miyamoto T, Yakushiji H, Ohno S, Miyake Y, Sakaguchi T, et al. Effects of N-[N-(3, 5-difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT) on cell proliferation and apoptosis in Ishikawa endometrial cancer cells. Hum Cell. 2012;25:9–15.CrossRefPubMed
38.
Wei Y, Zhang Z, Liao H, Wu L, Wu X, Zhou D, et al. Nuclear estrogen receptor-mediated Notch signaling and GPR30-mediated PI3K/AKT signaling in the regulation of endometrial cancer cell proliferation. Oncol Rep. 2012;27:504–10.PubMed
39.
Uemura T, Shepherd S, Ackerman L, Jan LY, Jan YN. Numb, a gene required in determination of cell fate during sensory organ formation in Drosophila embryos. Cell. 1989;58:349–60.CrossRefPubMed
40.
Rasin MR, Gazula VR, Breunig JJ, Kwan KY, Johnson MB, Liu-Chen S, et al. Numb and Numbl are required for maintenance of cadherin-based adhesion and polarity of neural progenitors. Nat Neurosci. 2007;10:819–27.CrossRefPubMed
41.
42.
Rennstam K, Mcmichael N, Berglund P, Honeth G, Hegardt C, Ryden L, et al. Numb protein expression correlates with a basal-like phenotype and cancer stem cell markers in primary breast cancer. Breast Cancer Res Treat. 2010;122:315–24.CrossRefPubMed
43.
Maiorano E, Favia G, Pece S, Resta L, Maisonneuve P, Di Fiore PP, et al. Prognostic implications of NUMB immunoreactivity in salivary gland carcinomas. Int J Immunopathol Pharmacol. 2007;20:779–89.PubMed
44.
Yan B, Omar FM, Das K, Ng WH, Lim C, Shiuan K, et al. Characterization of Numb expression in astrocytomas. Neuropathology. 2008;28:479–84.CrossRefPubMed
45.
Chen H, Chen X, Ye F, Lu W, Xie X. Symmetric division and expression of its regulatory gene Numb in human cervical squamous carcinoma cells. Pathobiology. 2009;76:149–54.CrossRefPubMed
46.
Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002;2:442–54.CrossRefPubMed
47.
Nieto MA. The snail superfamily of zinc-finger transcription factors. Nat Rev Mol Cell Biol. 2002;3:155–66.CrossRefPubMed
48.
Chenfang Dong YW. Jun Yao, Yifan Wang, Yinhua Yu, Piotr G. Rychahou, B. Mark Evers, Binhua P. Zhou: G9a interacts with Snail and is critical for Snail-mediated E-cadherin repression in human breast cancer. J Clin Invest. 2012;122(4):1469–86.PubMedCentralCrossRefPubMed
49.
Pon YL, Zhou HY, Cheung AN, Ngan HY, Wong AS. p70 S6 kinase promotes epithelial to mesenchymal transition through snail induction in ovarian cancer cells. Cancer Res. 2008;68:6524–32.CrossRefPubMed
50.
Kudo-Saito C, Shirako H, Takeuchi T, Kawakami Y. Cancer metastasis is accelerated through immunosuppression during Snail-induced EMT of cancer cells. Cancer Cell. 2009;15:195–206.CrossRefPubMed
51.
Haslehurst AM, Koti M, Dharsee M, Nuin P, Evans K, Geraci J, et al. EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer. BMC Cancer. 2012;12:91.PubMedCentralCrossRefPubMed
52.
Medici D, Hay ED, Olsen BR. Snail and Slug promote epithelial-mesenchymal transition through beta-catenin-T-cell factor-4-dependent expression of transforming growth factor-beta3. Mol Biol Cell. 2008;19:4875–87.PubMedCentralCrossRefPubMed
53.
Olmeda D, Montes A, Moreno-Bueno G, Flores JM, Portillo F, Cano A. Snai1 and Snai2 collaborate on tumor growth and metastasis properties of mouse skin carcinoma cell lines. Oncogene. 2008;27:4690–701.CrossRefPubMed
54.
Qian X, Anzovino A, Kim S, Suyama K, Yao J, Hulit J, et al. N-cadherin/FGFR promotes metastasis through epithelial-to-mesenchymal transition and stem/progenitor cell-like properties. Oncogene. 2014;33:3411–21.PubMedCentralCrossRefPubMed
55.
56.
Putzke AP, Ventura AP, Bailey AM, Akture C, Opoku-Ansah J, Celiktas M, et al. Metastatic progression of prostate cancer and e-cadherin regulation by zeb1 and SRC family kinases. Am J Pathol. 2011;179:400–10.PubMedCentralCrossRefPubMed
57.
Deep G, Jain AK, Ramteke A, Ting H, Vijendra KC, Gangar SC, et al. SNAI1 is critical for the aggressiveness of prostate cancer cells with low E-cadherin. Mol Cancer. 2014;13:37.PubMedCentralCrossRefPubMed
Metadata
Title
Aberrant expression of Notch1/numb/snail signaling, an epithelial mesenchymal transition related pathway, in adenomyosis
Authors
Shasha Qi
Xingbo Zhao
Mingjiang Li
Xiaohui Zhang
Zhenzhen Lu
Chunrun Yang
Chunhua Zhang
Hui Zhang
Na Zhang
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2015
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-015-0084-2

Other articles of this Issue 1/2015

Reproductive Biology and Endocrinology 1/2015 Go to the issue

Research

Regulation of kisspeptin and gonadotropin-releasing hormone expression in rat placenta: study using primary cultures of rat placental cells

Research

Resveratrol relieves gestational diabetes mellitus in mice through activating AMPK

Research

Cord blood adipokines, neonatal anthropometrics and postnatal growth in offspring of Hispanic and Native American women with diabetes mellitus

Research

What is the value of anti-Müllerian hormone in predicting the response to ovarian stimulation with GnRH agonist and antagonist protocols?

Research

Dynamic alteration of serum testosterone with aging: a cross-sectional study from Shanghai, China

Research

Some aspects of interactivity between endocrine and immune systems required for successful reproduction