{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:11:23Z","timestamp":1792638683315,"version":"4.5.0"},"reference-count":32,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2013,8,12]],"date-time":"2013-08-12T00:00:00Z","timestamp":1376265600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:p>Cancer development is often preceded by the appearance of preneoplastic lesions. In gastric carcinogenesis, chronic inflammation and histopathologic progression of the stomach epithelium lead to the development of metaplasia and eventually adenocarcinoma. The cell surface protein <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>44, especially its variant isoforms (<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>44v), has been implicated in metaplasia\u2013carcinoma sequence progression in the stomach. We recently found that <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>44v interacts with and stabilizes x<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>, a subunit of the cystine transporter system xc(\u2013), in cancer cells and thereby increases cystine uptake and confers resistance to various types of cellular stress <jats:italic>in vivo<\/jats:italic>. The functional relevance of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>44v and x<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> in the development of preneoplastic lesions, however, has remained unknown. We have now examined the role of the <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>44v\u2010x<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> system in the development of spasmolytic polypeptide\u2010expressing metaplasia (<jats:styled-content style=\"fixed-case\">SPEM<\/jats:styled-content>) in mouse models of gastric carcinogenesis. <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>44v was found to be expressed de novo in <jats:styled-content style=\"fixed-case\">SPEM<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>44v<jats:sup>+<\/jats:sup> metaplastic cells manifested upregulation of x<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> expression compared with <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>44v<jats:sup>\u2212<\/jats:sup> cells. Genetic ablation of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>44 or treatment with sulfasalazine, an inhibitor of x<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>\u2010dependent cystine transport, suppressed the development of <jats:styled-content style=\"fixed-case\">SPEM<\/jats:styled-content> and subsequent gastric tumor growth. Therapy targeted to <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>44v\u2010x<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> could thus prove effective for prevention or attenuation of the <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>44v\u2010dependent development of preneoplastic lesions and cancer.<\/jats:p>","DOI":"10.1111\/cas.12236","type":"journal-article","created":{"date-parts":[[2013,7,15]],"date-time":"2013-07-15T07:58:46Z","timestamp":1373875126000},"page":"1323-1329","source":"Crossref","is-referenced-by-count":101,"title":["Functional role of <scp>CD<\/scp>44v\u2010x<scp>CT<\/scp> system in the development of spasmolytic polypeptide\u2010expressing metaplasia"],"prefix":"10.1111","volume":"104","author":[{"given":"Takeyuki","family":"Wada","sequence":"first","affiliation":[{"name":"Division of Gene Regulation Institute for Advanced Medical Research Tokyo Japan"},{"name":"Department of Surgery School of Medicine 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