{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:22:20Z","timestamp":1790522540034,"version":"4.1.0"},"reference-count":41,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T00:00:00Z","timestamp":1485907200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Tumour Biol."],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:p>\n                    Gastrointestinal stromal tumors originate from interstitial cells of Cajal, the pacemaker cells of the gut. Ca\n                    <jats:sup>2+<\/jats:sup>\n                    regulates the pacemaker activity of interstitial cells of Cajal. Store-operated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry mediates the majority of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry in most cancer cells and may be a factor in regulating intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    in interstitial cells of Cajal and gastrointestinal stromal tumors. Therefore, a blockade of this mechanism may affect the progression of gastrointestinal stromal tumors. Orai1 is the pore subunit of store-operated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channels. Here, we reported that Orai1 was overexpressed in gastrointestinal stromal tumor tissues and was positively correlated with a high-risk grade in gastrointestinal stromal tumor patients. Furthermore, upon Orai1 silencing, the functional store-operated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry in gastrointestinal stromal tumor cells was decreased, indicating that the function of store-operated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry was mediated by Orai1. Inhibition of Orai1-mediated store-operated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry by Orai1 silencing or store-operated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry blockers (SKF-96365 and 2-aminoethyl diphenylborate) induced obvious cell proliferation suppression, cell-cycle distribution, and apoptosis stimulation in GIST-T1 cells. Conversely, Orai1 overexpression increased store-operated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry and cell proliferation in GIST882 cells. In addition, we found that activation of c-KIT and the extracellular signal\u2013regulated kinase pathway participated in the oncogenic functions of Orai1-mediated store-operated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry in gastrointestinal stromal tumor cells. These results revealed that Orai1-mediated store-operated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry is critical for gastrointestinal stromal tumor cell proliferation via c-KIT and ERK signaling pathway activation. Orai1-mediated store-operated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry plays an oncogenic role and may be a novel prognostic factor and therapeutic target for patients with gastrointestinal stromal tumors.\n                  <\/jats:p>","DOI":"10.1177\/1010428317691426","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T04:55:45Z","timestamp":1487912145000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":15,"title":["Orai1 mediates tumor-promoting store-operated Ca\n                    <sup>2+<\/sup>\n                    entry in human gastrointestinal stromal tumors via c-KIT and the extracellular signal\u2013regulated kinase pathway"],"prefix":"10.1177","volume":"39","author":[{"given":"Lei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijun","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 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