{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T01:59:44Z","timestamp":1793325584449,"version":"4.5.0"},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T00:00:00Z","timestamp":1579651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010882","name":"Tianjin Municipal Education Commission","doi-asserted-by":"publisher","award":["2018KJ070"],"award-info":[{"award-number":["2018KJ070"]}],"id":[{"id":"10.13039\/501100010882","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Endoplasmic reticulum stress exists within a tumor. Glucose\u2010regulated protein 94 (GRP94) is a stress\u2010induced chaperone protein involved in tumor development and progression. Its role in myeloma, colon cancer, and other tumors has been confirmed, but its role in lung cancer is unclear. This study aimed to determine the role of GRP94 in lung cancer progression and prognostic prediction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Immunohistochemical staining of GRP94 in human lung adenocarcinoma (AD) and corresponding normal tissue was performed, and its relationship with FOXP3<jats:sup>+<\/jats:sup> regulatory T\u2010cell (Treg) infiltration analyzed. We investigated the role of GRP94 in the behavior of lung AD cells by inhibiting <jats:italic>GRP94<\/jats:italic> expression in A549 cells. Western blotting was used to detect the TGF\u2010\u03b2\/SMAD2 signaling molecules and explore the possible molecular mechanism of GRP94.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>GRP94 mRNA (encoded by <jats:italic>HSP90B1<\/jats:italic>) and protein levels were upregulated and elevated, respectively, in lung AD compared to normal lung tissues. High GRP94 expression was associated with an advanced disease stage and poor survival. There was a positive correlation between GRP94 expression and FOXP3<jats:sup>+<\/jats:sup> Treg infiltration into lung AD tissues. Our results confirm that <jats:italic>GRP94<\/jats:italic> knockdown inhibits cell proliferation and promotes cell apoptosis by increasing caspase\u20107 and CHOP levels in lung AD cells. TGF\u2010\u03b2 and SMAD2 protein levels were decreased after GRP94 depletion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study revealed that that GRP94 expression in lung AD favors tumor progression and predicts poor prognosis. The oncogenic role of GRP94 may involve inducing Treg infiltration by promoting the TGF\u2010\u03b2 signaling pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>GRP94 protein levels were elevated in lung AD tissues compared to normal lung tissues. The high expression of <jats:italic>GRP94<\/jats:italic> in lung AD favors tumor progression and predicts poor prognosis.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The oncogenic role of the molecule GRP94 may involve the stimulation of Treg infiltration <jats:italic>via<\/jats:italic> promotion of the TGF\u2010\u03b2 signaling pathway.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1111\/1759-7714.13321","type":"journal-article","created":{"date-parts":[[2020,1,23]],"date-time":"2020-01-23T07:06:44Z","timestamp":1579763204000},"page":"704-712","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Overexpression of molecule GRP94 favors tumor progression in lung adenocarcinoma by interaction with regulatory T cells"],"prefix":"10.1111","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7018-3928","authenticated-orcid":false,"given":"Xiao\u2010Feng","family":"Duan","sequence":"first","affiliation":[{"name":"Department of Minimally Invasive Esophageal Surgery, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer Tianjin Medical University Cancer Hospital and Institute  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Wei","family":"Xin","sequence":"additional","affiliation":[{"name":"The Second Hospital of Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21442"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21338"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30958-8"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","unstructured":"RozpedekW PytelD MuchaBet al.The role of the PERK\/eIF2alpha\/ATF4\/CHOP signaling pathway in tumor progression during endoplasmic reticulum stress.Curr Mol 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