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Clinical and Translational Oncology
Published in: Clinical and Translational Oncology 10/2012

01-10-2012 | Educational Series – BLUE SERIES

The EMT signaling pathways in endometrial carcinoma

Authors: Eva Colas, Nuria Pedrola, Laura Devis, Tugçe Ertekin, Irene Campoy, Elena Martínez, Marta Llauradó, Marina Rigau, Mireia Olivan, Marta Garcia, Silvia Cabrera, Antonio Gil-Moreno, Jordi Xercavins, Josep Castellvi, Angel Garcia, Santiago Ramon y Cajal, Gema Moreno-Bueno, Xavier Dolcet, Francesc Alameda, Jose Palacios, Jaime Prat, Andreas Doll, Xavier Matias-Guiu, Miguel Abal, Jaume Reventos

Published in: Clinical and Translational Oncology | Issue 10/2012

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Abstract

Endometrial cancer (EC) is the most common gynecologic malignancy of the female genital tract and the fourth most common neoplasia in women. In EC, myometrial invasion is considered one of the most important prognostic factors. For this process to occur, epithelial tumor cells need to undergo an epithelial to mesenchymal transition (EMT), either transiently or stably, and to differing degrees. This process has been extensively described in other types of cancer but has been poorly studied in EC. In this review, several features of EMT and the main molecular pathways responsible for triggering this process are investigated in relation to EC. The most common hallmarks of EMT have been found in EC, either at the level of E-cadherin loss or at the induction of its repressors, as well as other molecular alterations consistent with the mesenchymal phenotype-like L1CAM and BMI-1 up-regulation. Pathways including progesterone receptor, TGFβ, ETV5 and microRNAs are deeply related to the EMT process in EC.
Literature
1.
2.
3.
4.
5.
6.
7.
Abal M et al (2007) Molecular determinants of invasion in endometrial cancer. Clin Transl Oncol 9:272–277PubMedCrossRef
8.
9.
Moreno-Bueno G, Portillo F, Cano A (2008) Transcriptional regulation of cell polarity in EMT and cancer. Oncogene 27:6958–6969PubMedCrossRef
10.
Yang J, Weinberg RA (2008) Epithelial–mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell 14:818–829PubMedCrossRef
11.
12.
Kang Y, Massague J (2004) Epithelial–mesenchymal transitions: twist in development and metastasis. Cell 118:277–279PubMedCrossRef
13.
Mueller MM, Fusenig NE (2004) Friends or foes—bipolar effects of the tumour stroma in cancer. Nat Rev Cancer 4:839–849PubMedCrossRef
14.
Bhowmick NA, Neilson EG, Moses HL (2004) Stromal fibroblasts in cancer initiation and progression. Nature 432:332–337PubMedCrossRef
15.
Barrallo-Gimeno A, Nieto MA (2005) The Snail genes as inducers of cell movement and survival: implications in development and cancer. Development 132:3151–3161PubMedCrossRef
16.
De Craene B, van Roy F, Berx G (2005) Unraveling signaling cascades for the Snail family of transcription factors. Cell Signal 17:535–547PubMedCrossRef
17.
Huber M, Kraut N, Beug H (2005) Molecular requirements for epithelial–mesenchymal transition during tumor progression. Curr Opin Cell Biol 17:548–558PubMedCrossRef
18.
Thiery JP, Sleeman JP (2006) Complex networks orchestrate epithelial–mesenchymal transitions. Nat Rev Mol Cell Biol 7:131–142PubMedCrossRef
19.
Micalizzi D, Farabaugh S, Ford H (2010) Epithelial–mesenchymal transition in cancer: parallels between normal development and tumor progression. J Mammary Gland Biol Neoplasia 15:117–134PubMedCrossRef
20.
Hurt EM, Saykally JN, Anose BM, Kalli KR, Sanders MM (2008) Expression of the ZEB1 (deltaEF1) transcription factor in human: additional insights. Mol Cell Biochem 318:89–99PubMedCrossRef
21.
Singh M et al (2008) ZEB1 expression in type I vs type II endometrial cancers: a marker of aggressive disease. Mod Pathol 21:912–923PubMedCrossRef
22.
Kyo S et al (2006) High Twist expression is involved in infiltrative endometrial cancer and affects patient survival. Hum Pathol 37:431–438PubMedCrossRef
23.
Blechschmidt K et al (2007) The E-cadherin repressor snail plays a role in tumor progression of endometrioid adenocarcinomas. Diagn Mol Pathol 16:222–228PubMedCrossRef
24.
Shih H-C et al (2004) Immunohistochemical expression of E-cadherin and beta-catenin in the normal and malignant human endometrium: an inverse correlation between E-cadherin and nuclear beta-catenin expression. Anticancer Res 24:3843–3850PubMed
25.
Scholten AN, Aliredjo R, Creutzberg CL, Smit VTHB (2006) Combined E-cadherin, alpha-catenin, and beta-catenin expression is a favorable prognostic factor in endometrial carcinoma. Int J Gynecol Cancer 16:1379–1385PubMedCrossRef
26.
Sakuragi N et al (1994) Decreased E-cadherin expression in endometrial carcinoma is associated with tumor dedifferentiation and deep myometrial invasion. Gynecol Oncol 53:183–189PubMedCrossRef
27.
Moreno-Bueno G et al (2003) Abnormalities of E- and P-cadherin and catenin (beta-, gamma-catenin, and p120ctn) expression in endometrial cancer and endometrial atypical hyperplasia. J Pathol 199:471–478PubMedCrossRef
28.
Stefansson IM, Salvesen HB, Akslen LA (2004) Prognostic impact of alterations in P-cadherin expression and related cell adhesion markers in endometrial cancer. J Clin Oncol 22:1242–1252PubMedCrossRef
29.
Mell LK et al (2004) Prognostic significance of E-cadherin protein expression in pathological stage I–III endometrial cancer. Clin Cancer Res 10:5546–5553PubMedCrossRef
30.
Leblanc M et al (2001) Alteration of CD44 and cadherins expression: possible association with augmented aggressiveness and invasiveness of endometrial carcinoma. Virchows Arch 438:78–85PubMedCrossRef
31.
Huszar M et al (2010) Up-regulation of L1CAM is linked to loss of hormone receptors and E-cadherin in aggressive subtypes of endometrial carcinomas. J Pathol 220:551–561PubMedCrossRef
32.
Pfeifer M et al (2010) L1CAM expression in endometrial carcinomas is regulated by usage of two different promoter regions. BMC Mol Biol 11:64PubMedCrossRef
33.
34.
Vonlanthen S et al (2001) The bmi-1 oncoprotein is differentially expressed in non-small cell lung cancer and correlates with INK4A-ARF locus expression. Br J Cancer 84:1372–1376PubMedCrossRef
35.
Guo B-H et al (2011) Bmi-1 promotes invasion and metastasis, and its elevated expression is correlated with an advanced stage of breast cancer. Mol. Cancer 10:10PubMedCrossRef
36.
Glinsky GV, Berezovska O, Glinskii AB (2005) Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. J Clin Invest 115:1503–1521PubMedCrossRef
37.
Zhang F, Sui L, Xin T (2008) Correlations of BMI-1 expression and telomerase activity in ovarian cancer tissues. Exp Oncol 30:70–74PubMed
38.
Honig A et al (2010) Overexpression of polycomb protein BMI-1 in human specimens of breast, ovarian, endometrial and cervical cancer. Anticancer Res 30:1559–1564PubMed
39.
Dong P et al (2011) MicroRNA-194 inhibits epithelial to mesenchymal transition of endometrial cancer cells by targeting oncogene BMI-1. Mol Cancer 10:99PubMedCrossRef
40.
Stewart CJR, Little L (2009) Immunophenotypic features of MELF pattern invasion in endometrial adenocarcinoma: evidence for epithelial–mesenchymal transition. Histopathology 55:91–101PubMedCrossRef
41.
Hanekamp EE et al (2005) Differences in invasive capacity of endometrial cancer cell lines expressing different progesterone receptor isotypes: possible involvement of cadherins. J Soc Gynecol Invest 12:278–284CrossRef
42.
Dai D, Wolf DM, Litman ES, White MJ, Leslie KK (2002) Progesterone inhibits human endometrial cancer cell growth and invasiveness: down-regulation of cellular adhesion molecules through progesterone B receptors. Cancer Res 62:881–886PubMed
43.
Hanekamp EE et al (2002) Loss of progesterone receptor may lead to an invasive phenotype in human endometrial cancer. Eur J Cancer 38(Suppl 6):S71–S72PubMedCrossRef
44.
Van der Horst PH et al (2012) Progesterone inhibits epithelial-to-mesenchymal transition in endometrial cancer. PLoS One 7(1):e30840
45.
Fujita N et al (2003) MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer. Cell 113:207–219PubMedCrossRef
46.
Dandachi N et al (2001) Co-expression of tenascin-C and vimentin in human breast cancer cells indicates phenotypic transdifferentiation during tumour progression: correlation with histopathological parameters, hormone receptors, and oncoproteins. J Pathol 193:181–189PubMedCrossRef
47.
Ehrlich CE, Young PC, Stehman FB, Sutton GP, Alford WM (1988) Steroid receptors and clinical outcome in patients with adenocarcinoma of the endometrium. Am J Obstet Gynecol 158:796–807PubMed
48.
Jeon Y-T et al (2006) Steroid receptor expressions in endometrial cancer: clinical significance and epidemiological implication. Cancer Lett 239:198–204PubMedCrossRef
49.
Thigpen JT et al (1999) Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group. J Clin Oncol 17:1736–1744PubMed
50.
Hanekamp EE et al (2003) Consequences of loss of progesterone receptor expression in development of invasive endometrial cancer. Clin Cancer Res 9:4190–4199PubMed
51.
Wang Y et al (2009) Progesterone inhibition of Wnt/beta-catenin signaling in normal endometrium and endometrial cancer. Clin Cancer Res 15:5784–5793PubMedCrossRef
52.
53.
Derynck R, Zhang YE (2003) Smad-dependent and Smad-independent pathways in TGF-beta family signaling. Nature 425:577–584PubMedCrossRef
54.
Parekh TV et al (2002) Transforming growth factor beta signaling is disabled early in human endometrial carcinogenesis concomitant with loss of growth inhibition. Cancer Res 62:2778–2790PubMed
55.
Muinelo-Romay L et al (2011) High-risk endometrial carcinoma profiling identifies TGF-β1 as a key factor in the initiation of tumor invasion. Mol Cancer Ther 10:1357–1366PubMedCrossRef
56.
Lei X, Wang L, Yang J, Sun L-Z (2009) TGFbeta signaling supports survival and metastasis of endometrial cancer cells. Cancer Manag Res 2009:15–24PubMed
57.
de Launoit Y et al (2006) The Ets transcription factors of the PEA3 group: transcriptional regulators in metastasis. Biochim Biophys Acta 1766:79–87PubMed
58.
Graves BJ, Petersen JM (1998) Specificity within the ets family of transcription factors. Adv Cancer Res 75:1–55PubMedCrossRef
59.
Planaguma J et al (2005) Up-regulation of ERM/ETV5 correlates with the degree of myometrial infiltration in endometrioid endometrial carcinoma. J Pathol 207:422–429PubMedCrossRef
60.
Llauradó M et al (2012) ETV5 transcription factor is overexpressed in ovarian cancer and regulates cell adhesion in ovarian cancer cells. Int J Cancer 130:1532–1543PubMedCrossRef
61.
62.
Monge M et al (2007) ERM/ETV5 up-regulation plays a role during myometrial infiltration through matrix metalloproteinase-2 activation in endometrial cancer. Cancer Res 67:6753–6759PubMedCrossRef
63.
Monge M et al (2009) Proteomic approach to ETV5 during endometrial carcinoma invasion reveals a link to oxidative stress. Carcinogenesis 30:1288–1297PubMedCrossRef
64.
Monge M et al (2009) Subtractive proteomic approach to the endometrial carcinoma invasion front. J Proteome Res 8:4676–4684PubMedCrossRef
65.
Ebert MS, Sharp PA (2012) Roles for MicroRNAs in conferring robustness to biological processes. Cell 149:515–524PubMedCrossRef
66.
67.
68.
Castilla MA et al (2011) Micro-RNA signature of the epithelial–mesenchymal transition in endometrial carcinosarcoma. J Pathol 223:72–80PubMedCrossRef
69.
Kong W et al (2008) MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA. Mol Cell Biol 28:6773–6784PubMedCrossRef
70.
Howe EN, Cochrane DR, Richer JK (2011) Targets of miR-200c mediate suppression of cell motility and anoikis resistance. Breast Cancer Res 13:R45PubMedCrossRef
71.
Cano A, Nieto MA (2008) Non-coding RNAs take centre stage in epithelial-to-mesenchymal transition. Trends Cell Biol 18:357–359PubMedCrossRef
Metadata
Title
The EMT signaling pathways in endometrial carcinoma
Authors
Eva Colas
Nuria Pedrola
Laura Devis
Tugçe Ertekin
Irene Campoy
Elena Martínez
Marta Llauradó
Marina Rigau
Mireia Olivan
Marta Garcia
Silvia Cabrera
Antonio Gil-Moreno
Jordi Xercavins
Josep Castellvi
Angel Garcia
Santiago Ramon y Cajal
Gema Moreno-Bueno
Xavier Dolcet
Francesc Alameda
Jose Palacios
Jaime Prat
Andreas Doll
Xavier Matias-Guiu
Miguel Abal
Jaume Reventos
Publication date
01-10-2012
Publisher
Springer Milan
Published in
Clinical and Translational Oncology / Issue 10/2012
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-012-0866-3

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