{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T21:29:28Z","timestamp":1774906168104,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,9,19]],"date-time":"2017-09-19T00:00:00Z","timestamp":1505779200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01\u2010CA185055"],"award-info":[{"award-number":["R01\u2010CA185055"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01\u2010DK106394"],"award-info":[{"award-number":["R01\u2010DK106394"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p>\n                    Zinc, an essential micronutrient, has a cancer preventive role. Zinc deficiency has been shown to contribute to the progression of esophageal cancer. Orai1, a store\u2010operated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry (SOCE) channel, was previously reported to be highly expressed in tumor tissues removed from patients with esophageal squamous cell carcinoma (ESCC) with poor prognosis, and elevation of its expression contributes to both hyperactive intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    oscillations and fast cell proliferation in human ESCC cells. However, the molecular basis of cancer preventive functions of zinc and its association with Orai1\u2010mediated cell proliferation remains unknown. The present study shows that zinc supplementation significantly inhibits proliferation of ESCC cell lines and that the effect of zinc is reversible with\n                    <jats:italic>N,N,N\u2032,N<\/jats:italic>\n                    \u2032\u2010tetrakis (2\u2010pyridylmethyl) ethylenediamine, a specific Zn\n                    <jats:sup>2+<\/jats:sup>\n                    chelator, whereas non\u2010 tumorigenic esophageal epithelial cells are significantly less sensitive to zinc treatment. Fluorescence live cell imaging revealed that extracellular Zn\n                    <jats:sup>2+<\/jats:sup>\n                    exerted rapid inhibitory effects on Orai1\u2010mediated SOCE and on intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    oscillations in the ESCC cells. Knockdown of Orai1 or expression of Orai1 mutants with compromised zinc binding significantly diminished sensitivity of the cancer cells to zinc treatment in both SOCE and cell proliferation analyses. These data suggest that zinc may inhibit cell proliferation of esophageal cancer cells through Orai1\u2010mediated intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    oscillations and reveal a possible molecular basis for zinc\u2010induced cancer prevention and Orai1\u2010SOCE signaling pathway in cancer cells.\u2014Choi, S., Cui, C., Luo, Y., Kim, S.\u2010H., Ko, J.\u2010K., Huo, X., Ma, J., Fu, L.\u2010W., Souza, R. F., Korichneva, I., Pan, Z. Selective inhibitory effects of zinc on cell proliferation in esophageal squamous cell carcinoma through Orai1. FASEB J. 32,404\u2010416 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201700227rrr","type":"journal-article","created":{"date-parts":[[2017,9,19]],"date-time":"2017-09-19T20:50:23Z","timestamp":1505854223000},"page":"404-416","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Selective inhibitory effects of zinc on cell proliferation in esophageal squamous cell carcinoma through Orai1"],"prefix":"10.1096","volume":"32","author":[{"given":"Sangyong","family":"Choi","sequence":"first","affiliation":[{"name":"College of Nursing and Health Innovation The University of Texas at Arlington Arlington Texas USA"},{"name":"Davis Heart and Lung Research Institute Ohio State University Wexner Medical Center Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaochu","family":"Cui","sequence":"additional","affiliation":[{"name":"College of Nursing and Health Innovation The University of Texas at Arlington Arlington Texas USA"},{"name":"Davis Heart and Lung Research Institute Ohio State University Wexner Medical Center Columbus Ohio USA"},{"name":"State Key Laboratory of Oncology in South China Collaborative Innovation Center of Cancer Medicine, Sun Yat\u2010Sen University Cancer Center Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhong","family":"Luo","sequence":"additional","affiliation":[{"name":"Davis Heart and Lung Research Institute Ohio State University Wexner Medical Center Columbus Ohio USA"},{"name":"Department of Endocrinology Children\u2032s Hospital of Chongqing Medical University Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun\u2010Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"Davis Heart and Lung Research Institute Ohio State University Wexner Medical Center Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae\u2010Kyun","family":"Ko","sequence":"additional","affiliation":[{"name":"Mutagenex Suwanee Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofang","family":"Huo","sequence":"additional","affiliation":[{"name":"Center for Esophageal Diseases, Baylor University Medical Center and Center for Esophageal Research, Baylor Scott and White Research Institute Dallas Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianjie","family":"Ma","sequence":"additional","affiliation":[{"name":"Davis Heart and Lung Research Institute Ohio State University Wexner Medical Center Columbus Ohio USA"},{"name":"Department of Surgery Ohio State University Wexner Medical Center Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li\u2010Wu","family":"Fu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China Collaborative Innovation Center of Cancer Medicine, Sun Yat\u2010Sen University Cancer Center Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rhonda F.","family":"Souza","sequence":"additional","affiliation":[{"name":"Center for Esophageal Diseases, Baylor University Medical Center and Center for Esophageal Research, Baylor Scott and White Research Institute Dallas Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Korichneva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Picardie Jules Verne Amiens France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zui","family":"Pan","sequence":"additional","affiliation":[{"name":"College of Nursing and Health Innovation The University of Texas at Arlington Arlington Texas USA"},{"name":"Davis Heart and Lung Research Institute Ohio State University Wexner Medical Center Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,9,19]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"esophageal cancer","year":"2016"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dji042"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra035010"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(99)00191-3"},{"key":"e_1_2_8_6_1","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.2174\/0929867322666150209153750","article-title":"Zinc\u2010permeable ion channels: effects on intracellular zinc dynamics and potential physiological\/pathophysiological significance","volume":"22","author":"Inoue K.","year":"2015","journal-title":"Curr. 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