and Epithelial Mesenchymal Transition in Human Gastric Cancers: An Update of the Literature

Overview

Journal Heliyon

Specialty Social Sciences

Date 2023 Aug 23

PMID 37609398

Authors

Tala M Jamal Eddin

Shahd M O Nasr

Ishita Gupta

Hatem Zayed

Ala-Eddin Al Moustafa

Affiliations

Soon will be listed here.

Abstract

Gastric cancer, a multifactorial disease, is considered one of the most common malignancies worldwide. In addition to genetic and environmental risk factors, infectious agents, such as Epstein-Barr virus (EBV) and () contribute to the onset and development of gastric cancer. is a type I carcinogen that colonizes the gastric epithelium of approximately 50% of the world's population, thus increasing the risk of gastric cancer development. On the other hand, epithelial mesenchymal transition (EMT) is a fundamental process crucial to embryogenic growth, wound healing, organ fibrosis and cancer progression. Several studies associate gastric pathogen infection of the epithelium with EMT initiation, provoking cancer metastasis in the gastric mucosa through various molecular signaling pathways. Additionally, EMT is implicated in the progression and development of -associated gastric cancer. In this review, we recapitulate recent findings elucidating the association between infection in EMT promotion leading to gastric cancer progression and metastasis.

Citing Articles

and gastric cancer: current insights and nanoparticle-based interventions.

Shah S, Mumtaz M, Sharif S, Mustafa I, Nayila I RSC Adv. 2025; 15(7):5558-5570.

PMID: 39967885 PMC: 11834156. DOI: 10.1039/d4ra07886a.

EFHD1 Activates SIK3 to Limit Colorectal Cancer Initiation and Progression via the Hippo Pathway.

Huang Q, Tang X, Gan C, Deng Q, Zhi S, Huang Q J Cancer. 2025; 16(4):1348-1362.

PMID: 39895792 PMC: 11786025. DOI: 10.7150/jca.103229.

and Variant Alleles Affect Susceptibility to Infection and Severity of -Associated Clinical Manifestations.

Pantic I, Lugonja S, Jerotic D, Pljesa-Ercegovac M, Matic M, Bakovic N Int J Mol Sci. 2025; 26(2.

PMID: 39859205 PMC: 11764725. DOI: 10.3390/ijms26020488.

Gastrointestinal cancer resistance to treatment: the role of microbiota.

Kolahi Sadeghi L, Vahidian F, Eterafi M, Safarzadeh E Infect Agent Cancer. 2024; 19(1):50.

PMID: 39369252 PMC: 11453072. DOI: 10.1186/s13027-024-00605-3.

The spatiotemporal associations between esophageal and gastric cancers provide evidence for its joint endoscopic screening in China: a population-based study.

Li P, Qi X, Bai R, Yang M, Jing J, Xia R BMC Med. 2024; 22(1):364.

PMID: 39232729 PMC: 11375892. DOI: 10.1186/s12916-024-03594-7.

References

Krishna M, Narang H . The complexity of mitogen-activated protein kinases (MAPKs) made simple. Cell Mol Life Sci. 2008; 65(22):3525-44. PMC: 11131782. DOI: 10.1007/s00018-008-8170-7. View

Yin Y, Grabowska A, Clarke P, Whelband E, Robinson K, Argent R . Helicobacter pylori potentiates epithelial:mesenchymal transition in gastric cancer: links to soluble HB-EGF, gastrin and matrix metalloproteinase-7. Gut. 2010; 59(8):1037-45. PMC: 2976077. DOI: 10.1136/gut.2009.199794. View

Guo L, Fang T, Jiang Y, Liu D . IRF7 is a Prognostic Biomarker and Associated with Immune Infiltration in Stomach Adenocarcinoma. Int J Gen Med. 2021; 14:9887-9902. PMC: 8687632. DOI: 10.2147/IJGM.S342607. View

Wen J, Wang Y, Gao C, Zhang G, You Q, Zhang W . Helicobacter pylori infection promotes Aquaporin 3 expression via the ROS-HIF-1α-AQP3-ROS loop in stomach mucosa: a potential novel mechanism for cancer pathogenesis. Oncogene. 2018; 37(26):3549-3561. DOI: 10.1038/s41388-018-0208-1. View

Sonkar C, Kashyap D, Varshney N, Baral B, Jha H . Impact of Gastrointestinal Symptoms in COVID-19: a Molecular Approach. SN Compr Clin Med. 2020; 2(12):2658-2669. PMC: 7609378. DOI: 10.1007/s42399-020-00619-z. View

Mitsuno Y, Yoshida H, Maeda S, Ogura K, Hirata Y, Kawabe T . Helicobacter pylori induced transactivation of SRE and AP-1 through the ERK signalling pathway in gastric cancer cells. Gut. 2001; 49(1):18-22. PMC: 1728350. DOI: 10.1136/gut.49.1.18. View

Takaishi S, Okumura T, Tu S, Wang S, Shibata W, Vigneshwaran R . Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells. 2009; 27(5):1006-20. PMC: 2746367. DOI: 10.1002/stem.30. View

Higashi H, Tsutsumi R, Fujita A, Yamazaki S, Asaka M, Azuma T . Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Proc Natl Acad Sci U S A. 2002; 99(22):14428-33. PMC: 137900. DOI: 10.1073/pnas.222375399. View

Tilahun M, Gedefie A, Belayhun C, Sahle Z, Abera A . Pathogenicity Islands and Cysteine Proteases in Role of Coinfection and Pathogenesis. Infect Drug Resist. 2022; 15:21-34. PMC: 8747529. DOI: 10.2147/IDR.S346705. View

10.

Mani S, Guo W, Liao M, Eaton E, Ayyanan A, Zhou A . The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008; 133(4):704-15. PMC: 2728032. DOI: 10.1016/j.cell.2008.03.027. View

11.

Carvalho J, Van Grieken N, Pereira P, Sousa S, Tijssen M, Buffart T . Lack of microRNA-101 causes E-cadherin functional deregulation through EZH2 up-regulation in intestinal gastric cancer. J Pathol. 2012; 228(1):31-44. DOI: 10.1002/path.4032. View

12.

Ribatti D, Tamma R, Annese T . Epithelial-Mesenchymal Transition in Cancer: A Historical Overview. Transl Oncol. 2020; 13(6):100773. PMC: 7182759. DOI: 10.1016/j.tranon.2020.100773. View

13.

Clevers H . Wnt/beta-catenin signaling in development and disease. Cell. 2006; 127(3):469-80. DOI: 10.1016/j.cell.2006.10.018. View

14.

Correa P . Gastric cancer: overview. Gastroenterol Clin North Am. 2013; 42(2):211-7. PMC: 3995345. DOI: 10.1016/j.gtc.2013.01.002. View

15.

Watanabe T, Asano N, Fichtner-Feigl S, Gorelick P, Tsuji Y, Matsumoto Y . NOD1 contributes to mouse host defense against Helicobacter pylori via induction of type I IFN and activation of the ISGF3 signaling pathway. J Clin Invest. 2010; 120(5):1645-62. PMC: 2860924. DOI: 10.1172/JCI39481. View

16.

Alves C, Rosivatz E, Schott C, Hollweck R, Becker I, Sarbia M . Slug is overexpressed in gastric carcinomas and may act synergistically with SIP1 and Snail in the down-regulation of E-cadherin. J Pathol. 2007; 211(5):507-515. DOI: 10.1002/path.2138. View

17.

Baj J, Korona-Glowniak I, Forma A, Maani A, Sitarz E, Rahnama-Hezavah M . Mechanisms of the Epithelial-Mesenchymal Transition and Tumor Microenvironment in -Induced Gastric Cancer. Cells. 2020; 9(4). PMC: 7225971. DOI: 10.3390/cells9041055. View

18.

Chen Z . Ubiquitin signalling in the NF-kappaB pathway. Nat Cell Biol. 2005; 7(8):758-65. PMC: 1551980. DOI: 10.1038/ncb0805-758. View

19.

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

20.

Ferreira R, Machado J, Figueiredo C . Clinical relevance of Helicobacter pylori vacA and cagA genotypes in gastric carcinoma. Best Pract Res Clin Gastroenterol. 2014; 28(6):1003-15. DOI: 10.1016/j.bpg.2014.09.004. View