Roles of E-cadherin and Noncoding RNAs in the Epithelial-mesenchymal Transition and Progression in Gastric Cancer

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2019 Jun 20

PMID 31212809

Citations 66

Authors

Irina V Bure

Marina V Nemtsova

Dmitry V Zaletaev

Affiliations

Soon will be listed here.

Abstract

The epithelial-mesenchymal transition (EMT) is thought to be at the root of invasive and metastatic cancer cell spreading. E-cadherin is an important player in this process, which forms the structures that establish and maintain cell-cell interactions. A partial or complete loss of E-cadherin expression in the EMT is presumably mediated by mechanisms that block the expression of E-cadherin regulators and involve the E-cadherin-associated transcription factors. The protein is involved in several oncogenic signaling pathways, such as the Wnt/β-catenin, Rho GTPase, and EGF/EGFR, whereby it plays a role in many tumors, including gastric cancer. Such noncoding transcripts as microRNAs and long noncoding RNAs-critical components of epigenetic control of gene expression in carcinogenesis-contribute to regulation of the E-cadherin function by acting directly or through numerous factors controlling transcription of its gene, and thus affecting not only cancer cell proliferation and metastasis, but also the EMT. This review focuses on the role of E-cadherin and the non-coding RNAs-mediated mechanisms of its expressional control in the EMT during stomach carcinogenesis.

Citing Articles

Integrative bioinformatics analysis of high-throughput sequencing and in vitro functional analysis leads to uncovering key hub genes in esophageal squamous cell carcinoma.

Shen F, Liu X, Ding F, Yu Z, Shi X, Cheng L Hereditas. 2025; 162(1):38.

PMID: 40087784 DOI: 10.1186/s41065-025-00398-4.

Homoharringtonine: mechanisms, clinical applications and research progress.

Wang W, He L, Lin T, Xiang F, Wu Y, Zhou F Front Oncol. 2025; 15:1522273.

PMID: 39949739 PMC: 11821653. DOI: 10.3389/fonc.2025.1522273.

Highly expressed B3GALT5-AS1 contributes to gastric cancer progression by recruiting WDR5 to mediate B3GALT5 and regulating β-catenin/ZEB1 axis.

Feng W, Tang Y, Jing R, Ju S, Zong W J Cell Mol Med. 2024; 28(17):e70061.

PMID: 39224045 PMC: 11369489. DOI: 10.1111/jcmm.70061.

Notch1 signaling pathway promotes growth and metastasis of gastric cancer via modulating CDH5.

Zhou L, Yang Y, Ye Y, Qiao Q, Mi Y, Liu H Aging (Albany NY). 2024; 16(16):11893-11903.

PMID: 39172098 PMC: 11386911. DOI: 10.18632/aging.206061.

The regulatory mechanism of m6A modification in gastric cancer.

Wu S, Li C, Zhou H, Yang Y, Liang N, Fu Y Discov Oncol. 2024; 15(1):283.

PMID: 39009956 PMC: 11250764. DOI: 10.1007/s12672-024-00994-2.

References

Suriano G, Oliveira M, Huntsman D, Mateus A, Ferreira P, Casares F . E-cadherin germline missense mutations and cell phenotype: evidence for the independence of cell invasion on the motile capabilities of the cells. Hum Mol Genet. 2003; 12(22):3007-16. DOI: 10.1093/hmg/ddg316. View

Cavallaro U, Christofori G . Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nat Rev Cancer. 2004; 4(2):118-32. DOI: 10.1038/nrc1276. View

Pan Y, Bi F, Liu N, Xue Y, Yao X, Zheng Y . Expression of seven main Rho family members in gastric carcinoma. Biochem Biophys Res Commun. 2004; 315(3):686-91. DOI: 10.1016/j.bbrc.2004.01.108. View

Kuphal S, Poser I, Jobin C, Hellerbrand C, Bosserhoff A . Loss of E-cadherin leads to upregulation of NFkappaB activity in malignant melanoma. Oncogene. 2004; 23(52):8509-19. DOI: 10.1038/sj.onc.1207831. View

Mattick J, Makunin I . Non-coding RNA. Hum Mol Genet. 2006; 15 Spec No 1:R17-29. DOI: 10.1093/hmg/ddl046. View

Christiansen J, Rajasekaran A . Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res. 2006; 66(17):8319-26. DOI: 10.1158/0008-5472.CAN-06-0410. View

Taft R, Pheasant M, Mattick J . The relationship between non-protein-coding DNA and eukaryotic complexity. Bioessays. 2007; 29(3):288-99. DOI: 10.1002/bies.20544. View

Mateus A, Seruca R, Machado J, Keller G, Oliveira M, Suriano G . EGFR regulates RhoA-GTP dependent cell motility in E-cadherin mutant cells. Hum Mol Genet. 2007; 16(13):1639-47. DOI: 10.1093/hmg/ddm113. View

Bremm A, Walch A, Fuchs M, Mages J, Duyster J, Keller G . Enhanced activation of epidermal growth factor receptor caused by tumor-derived E-cadherin mutations. Cancer Res. 2008; 68(3):707-14. DOI: 10.1158/0008-5472.CAN-07-1588. View

10.

Heasman S, Ridley A . Mammalian Rho GTPases: new insights into their functions from in vivo studies. Nat Rev Mol Cell Biol. 2008; 9(9):690-701. DOI: 10.1038/nrm2476. View

11.

Soto E, Yanagisawa M, Marlow L, Copland J, Perez E, Anastasiadis P . p120 catenin induces opposing effects on tumor cell growth depending on E-cadherin expression. J Cell Biol. 2008; 183(4):737-49. PMC: 2582886. DOI: 10.1083/jcb.200805113. View

12.

Cowell C, Yan I, Eiseler T, Leightner A, Doppler H, Storz P . Loss of cell-cell contacts induces NF-kappaB via RhoA-mediated activation of protein kinase D1. J Cell Biochem. 2009; 106(4):714-28. PMC: 4556359. DOI: 10.1002/jcb.22067. View

13.

Mercer T, Dinger M, Mattick J . Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009; 10(3):155-9. DOI: 10.1038/nrg2521. View

14.

Kalluri R, Weinberg R . The basics of epithelial-mesenchymal transition. J Clin Invest. 2009; 119(6):1420-8. PMC: 2689101. DOI: 10.1172/JCI39104. View

15.

Polk D, Peek Jr R . Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer. 2010; 10(6):403-14. PMC: 2957472. DOI: 10.1038/nrc2857. View

16.

Yamashita M, Toyota M, Suzuki H, Nojima M, Yamamoto E, Kamimae S . DNA methylation of interferon regulatory factors in gastric cancer and noncancerous gastric mucosae. Cancer Sci. 2010; 101(7):1708-16. PMC: 11158968. DOI: 10.1111/j.1349-7006.2010.01581.x. View

17.

Khaitan D, Dinger M, Mazar J, Crawford J, Smith M, Mattick J . The melanoma-upregulated long noncoding RNA SPRY4-IT1 modulates apoptosis and invasion. Cancer Res. 2011; 71(11):3852-62. DOI: 10.1158/0008-5472.CAN-10-4460. View

18.

Ben-Neriah Y, Karin M . Inflammation meets cancer, with NF-κB as the matchmaker. Nat Immunol. 2011; 12(8):715-23. DOI: 10.1038/ni.2060. View

19.

Fukayama M, Ushiku T . Epstein-Barr virus-associated gastric carcinoma. Pathol Res Pract. 2011; 207(9):529-37. DOI: 10.1016/j.prp.2011.07.004. View

20.

Sivakumaran S, Agakov F, Theodoratou E, Prendergast J, Zgaga L, Manolio T . Abundant pleiotropy in human complex diseases and traits. Am J Hum Genet. 2011; 89(5):607-18. PMC: 3213397. DOI: 10.1016/j.ajhg.2011.10.004. View