The EMT Signaling Pathways in Endometrial Carcinoma

Overview

Journal Clin Transl Oncol

Specialty Oncology

Date 2012 Aug 23

PMID 22911547

Citations 56

Authors

Eva Colas

Nuria Pedrola

Laura Devis

Tugce Ertekin

Irene Campoy

Elena Martinez

Marta Llaurado

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

Affiliations

Soon will be listed here.

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.

Citing Articles

TUBB2B regulates epithelial-mesenchymal transition via interaction with Vimentin to promote glioma migration and invasion.

Li J, Zhou Z, Zhang J, Wang M, Luan X, Zhao M Cancer Cell Int. 2024; 24(1):423.

PMID: 39707368 PMC: 11662515. DOI: 10.1186/s12935-024-03618-5.

Palmitic Acid Exerts Anti-Tumorigenic Activities by Modulating Cellular Stress and Lipid Droplet Formation in Endometrial Cancer.

Zhao Z, Wang J, Kong W, Newton M, Burkett W, Sun W Biomolecules. 2024; 14(5).

PMID: 38786008 PMC: 11117634. DOI: 10.3390/biom14050601.

Genome-Wide Association Studies and Runs of Homozygosity to Identify Reproduction-Related Genes in Yorkshire Pig Population.

Zhang L, Zhang S, Yuan M, Zhan F, Song M, Shang P Genes (Basel). 2023; 14(12).

PMID: 38136955 PMC: 10742578. DOI: 10.3390/genes14122133.

Targeting c-MYC: a potential non-hormonal therapeutic approach for endometriosis treatment.

Nothnick W, Arachchige S, Minchella P, Stephens E, Graham A Front Cell Dev Biol. 2023; 11:1225055.

PMID: 38078012 PMC: 10702580. DOI: 10.3389/fcell.2023.1225055.

Combined PI3K Inhibitor and Eribulin Enhances Anti-Tumor Activity in Preclinical Models of Paclitaxel-Resistant, PIK3CA-Mutated Endometrial Cancer.

Jeong Y, Katuwal N, Kang M, Ghosh M, Hong S, Park S Cancers (Basel). 2023; 15(19).

PMID: 37835582 PMC: 10571568. DOI: 10.3390/cancers15194887.

References

Bokhman J . Two pathogenetic types of endometrial carcinoma. Gynecol Oncol. 1983; 15(1):10-7. DOI: 10.1016/0090-8258(83)90111-7. View

Planaguma J, Abal M, Gil-Moreno A, Diaz-Fuertes M, Monge M, Garcia A . Up-regulation of ERM/ETV5 correlates with the degree of myometrial infiltration in endometrioid endometrial carcinoma. J Pathol. 2005; 207(4):422-9. DOI: 10.1002/path.1853. View

Mueller M, Fusenig N . Friends or foes - bipolar effects of the tumour stroma in cancer. Nat Rev Cancer. 2004; 4(11):839-49. DOI: 10.1038/nrc1477. View

Thiery J, Sleeman J . Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 2006; 7(2):131-42. DOI: 10.1038/nrm1835. View

Moreno-Bueno G, Hardisson D, Sarrio D, Sanchez C, Cassia R, Prat J . Abnormalities of E- and P-cadherin and catenin (beta-, gamma-catenin, and p120ctn) expression in endometrial cancer and endometrial atypical hyperplasia. J Pathol. 2003; 199(4):471-8. DOI: 10.1002/path.1310. View

Huber M, Kraut N, Beug H . Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol. 2005; 17(5):548-58. DOI: 10.1016/j.ceb.2005.08.001. View

Hanekamp E, Gielen S, de Ruiter P, Chadha-Ajwani S, Huikeshoven F, Burger C . Differences in invasive capacity of endometrial cancer cell lines expressing different progesterone receptor isotypes: possible involvement of cadherins. J Soc Gynecol Investig. 2005; 12(4):278-84. DOI: 10.1016/j.jsgi.2005.01.030. View

Sakuragi N, Nishiya M, Ikeda K, Ohkouch T, Furth E, Hareyama H . Decreased E-cadherin expression in endometrial carcinoma is associated with tumor dedifferentiation and deep myometrial invasion. Gynecol Oncol. 1994; 53(2):183-9. DOI: 10.1006/gyno.1994.1113. View

Yeramian A, Moreno-Bueno G, Dolcet X, Catasus L, Abal M, Colas E . Endometrial carcinoma: molecular alterations involved in tumor development and progression. Oncogene. 2012; 32(4):403-13. DOI: 10.1038/onc.2012.76. View

10.

Graves B, Petersen J . Specificity within the ets family of transcription factors. Adv Cancer Res. 1998; 75:1-55. DOI: 10.1016/s0065-230x(08)60738-1. View

11.

Derynck R, Zhang Y . Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 2003; 425(6958):577-84. DOI: 10.1038/nature02006. View

12.

Zhang F, Sui L, Xin T . Correlations of BMI-1 expression and telomerase activity in ovarian cancer tissues. Exp Oncol. 2008; 30(1):70-4. View

13.

Llaurado M, Ruiz A, Majem B, Ertekin T, Colas E, Pedrola N . Molecular bases of endometrial cancer: new roles for new actors in the diagnosis and the therapy of the disease. Mol Cell Endocrinol. 2011; 358(2):244-55. DOI: 10.1016/j.mce.2011.10.003. View

14.

Kyo S, Sakaguchi J, Ohno S, Mizumoto Y, Maida Y, Hashimoto M . High Twist expression is involved in infiltrative endometrial cancer and affects patient survival. Hum Pathol. 2006; 37(4):431-8. DOI: 10.1016/j.humpath.2005.12.021. View

15.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

16.

Thigpen J, Brady M, Alvarez R, Adelson M, Homesley H, Manetta A . Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group. J Clin Oncol. 1999; 17(6):1736-44. DOI: 10.1200/JCO.1999.17.6.1736. View

17.

Wang Y, Hanifi-Moghaddam P, Hanekamp E, Kloosterboer H, Franken P, Veldscholte J . Progesterone inhibition of Wnt/beta-catenin signaling in normal endometrium and endometrial cancer. Clin Cancer Res. 2009; 15(18):5784-93. DOI: 10.1158/1078-0432.CCR-09-0814. View

18.

Scholten A, Aliredjo R, Creutzberg C, Smit V . Combined E-cadherin, alpha-catenin, and beta-catenin expression is a favorable prognostic factor in endometrial carcinoma. Int J Gynecol Cancer. 2006; 16(3):1379-85. DOI: 10.1111/j.1525-1438.2006.00406.x. View

19.

Honig A, Weidler C, Hausler S, Krockenberger M, Buchholz S, Koster F . Overexpression of polycomb protein BMI-1 in human specimens of breast, ovarian, endometrial and cervical cancer. Anticancer Res. 2010; 30(5):1559-64. View

20.

Monge M, Colas E, Doll A, Gonzalez M, Gil-Moreno A, Planaguma J . ERM/ETV5 up-regulation plays a role during myometrial infiltration through matrix metalloproteinase-2 activation in endometrial cancer. Cancer Res. 2007; 67(14):6753-9. DOI: 10.1158/0008-5472.CAN-06-4487. View