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Review
. 2022 Jan 7;14(2):290.
doi: 10.3390/cancers14020290.

Claudins and Gastric Cancer: An Overview

Itaru Hashimoto  1   2 , Takashi Oshima  1
Affiliations
Review

Claudins and Gastric Cancer: An Overview

Itaru Hashimoto et al. Cancers (Basel). .

Abstract

Despite recent improvements in diagnostic ability and treatment strategies, advanced gastric cancer (GC) has a high frequency of recurrence and metastasis, with poor prognosis. To improve the treatment results of GC, the search for new treatment targets from proteins related to epithelial-mesenchymal transition (EMT) and cell-cell adhesion is currently being conducted. EMT plays an important role in cancer metastasis and is initiated by the loss of cell-cell adhesion, such as tight junctions (TJs), adherens junctions, desmosomes, and gap junctions. Among these, claudins (CLDNs) are highly expressed in some cancers, including GC. Abnormal expression of CLDN1, CLDN2, CLDN3, CLDN4, CLDN6, CLDN7, CLDN10, CLDN11, CLDN14, CLDN17, CLDN18, and CLDN23 have been reported. Among these, CLDN18 is of particular interest. In The Cancer Genome Atlas, GC was classified into four new molecular subtypes, and CLDN18-ARHGAP fusion was observed in the genomically stable type. An anti-CLDN18.2 antibody drug was recently developed as a therapeutic drug for GC, and the results of clinical trials are highly predictable. Thus, CLDNs are highly expressed in GC as TJs and are expected targets for new antibody drugs. Herein, we review the literature on CLDNs, focusing on CLDN18 in GC.

Keywords: CLDN18; claudin; gastric cancer; metastasis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic of the claudin protein located in tight junction and the 3D structures of CLDN4 (PDB: 7KP4). Adapted from “Cell Junction Types”, by BioRender.com (2021). Retrieved from https://app.biorender.com/biorender-templates (accessed on 30 September 2021).
Figure 2
Figure 2
Previous reports of CLDN18-ARHGAPs and schematic of CLDN18-ARHGAP protein. Created with BioRender.com.
See this image and copyright information in PMC

References

    1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660. - DOI - PubMed
    1. Riihimäki M., Hemminki A., Sundquist K., Sundquist J., Hemminki K. Metastatic Spread in Patients with Gastric Cancer. Oncotarget. 2016;7:52307–52316. doi: 10.18632/oncotarget.10740. - DOI - PMC - PubMed
    1. Li W., Ng J.M.-K., Wong C.C., Ng E.K.W., Yu J. Molecular Alterations of Cancer Cell and Tumour Microenvironment in Metastatic Gastric Cancer. Oncogene. 2018;37:4903–4920. doi: 10.1038/s41388-018-0341-x. - DOI - PMC - PubMed
    1. Lamouille S., Xu J., Derynck R. Molecular Mechanisms of Epithelial-Mesenchymal Transition. Nat. Rev. Mol. Cell Biol. 2014;15:178–196. doi: 10.1038/nrm3758. - DOI - PMC - PubMed
    1. Acloque H., Adams M.S., Fishwick K., Bronner-Fraser M., Nieto M.A. Epithelial-Mesenchymal Transitions: The Importance of Changing Cell State in Development and Disease. J. Clin. Investig. 2009;119:1438–1449. doi: 10.1172/JCI38019. - DOI - PMC - PubMed

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