{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T15:34:17Z","timestamp":1762529657841,"version":"build-2065373602"},"reference-count":34,"publisher":"Canadian Science Publishing","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":["cdnsciencepub.com"],"crossmark-restriction":false},"short-container-title":["Biochem. Cell Biol."],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"<jats:p>Our purpose was to explore the role and regulatory mechanisms of kringle containing transmembrane protein 2 (KREMEN2) in the development and progression of non-small cell lung cancer (NSCLC). KREMEN2 expression levels were higher in NSCLC tissues and cells than in normal tissues and cells. Down-regulation of KREMEN2 by siRNAs suppressed proliferation, migration, invasion, and epithelial mesenchymal transition (EMT), and accelerated apoptosis in NSCLC cells. Furthermore, KREMEN2 knockdown repressed PI3K\/AKT\/mTOR signaling, and KREMEN2 overexpression activated PI3K\/AKT\/mTOR signaling. Additionally, PI3K activator (740Y-P) treatment or PI3K overexpression reversed the inhibitory function of KREMEN2 knockdown on proliferation and metastasis, as well as the strengthened function of KREMEN2 knockdown on the apoptosis of NSCLC cells. Moreover, KREMEN2 suppressed tumor growth by inhibiting PI3K\/AKT\/mTOR signaling in mice. The pharmacologic inhibitor of KREMEN2 (genistein) was also demonstrated to suppress tumor growth in mice. In conclusion, our study suggested that KREMEN2 knockdown could repress the proliferative, migratory, and invasive capacity, as well as EMT, while accelerating the apoptotic capacity of NSCLC cells by inhibiting PI3K\/AKT\/mTOR signaling.<\/jats:p>","DOI":"10.1139\/bcb-2025-0039","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T21:36:11Z","timestamp":1752183371000},"page":"1-13","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["KREMEN2 promotes the proliferation and the metastasis through activating PI3K\/AKT\/mTOR signaling pathway in non-small cell lung cancer"],"prefix":"10.1139","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9012-2842","authenticated-orcid":false,"given":"Shunying","family":"Wang","sequence":"first","affiliation":[{"name":"Jinan City People's Hospital","place":["Jinan, P.R. China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Jinan City People's Hospital","place":["Jinan, P.R. China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenming","family":"Wang","sequence":"additional","affiliation":[{"name":"Jinan City People's Hospital","place":["Jinan, P.R. China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"155","reference":[{"key":"refg1\/ref1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.534095"},{"issue":"5","key":"refg2\/ref2","first-page":"1558","volume":"23","author":"Cihan Y.","year":"2018","journal-title":"J. B.U.ON.: Official J. Balkan Union Oncol."},{"key":"refg3\/ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2018.04.013"},{"key":"refg4\/ref4","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00154"},{"key":"refg5\/ref5","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-017-0980-8"},{"key":"refg6\/ref6","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20201870"},{"key":"refg7\/ref7","first-page":"34","volume":"71","author":"Gester F.","year":"2016","journal-title":"Rev. Med. Liege"},{"key":"refg8\/ref8","doi-asserted-by":"publisher","DOI":"10.1242\/dev.005942"},{"key":"refg9\/ref9","doi-asserted-by":"publisher","DOI":"10.1038\/nature25183"},{"key":"refg10\/ref10","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30958-8"},{"key":"refg11\/ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.labinv.2024.102059"},{"key":"refg12\/ref12","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27262"},{"key":"refg13\/ref13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010309"},{"key":"refg14\/ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.07.011"},{"key":"refg15\/ref15","doi-asserted-by":"publisher","DOI":"10.26355\/eurrev_202006_21509"},{"key":"refg16\/ref16","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.16643"},{"key":"refg17\/ref17","doi-asserted-by":"publisher","DOI":"10.3389\/pore.2023.1611082"},{"key":"refg18\/ref18","doi-asserted-by":"publisher","DOI":"10.1016\/s0378-1119(02)01106-x"},{"key":"refg19\/ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173282"},{"key":"refg20\/ref20","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-062913-051343"},{"key":"refg21\/ref21","doi-asserted-by":"publisher","DOI":"10.4065\/83.5.584"},{"key":"refg22\/ref22","doi-asserted-by":"publisher","DOI":"10.1016\/s0167-4781(01)00168-3"},{"key":"refg23\/ref23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2007.00201.x"},{"key":"refg24\/ref24","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i18.5403"},{"key":"refg25\/ref25","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy275"},{"key":"refg26\/ref26","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21387"},{"issue":"5","key":"refg27\/ref27","first-page":"226","volume":"157","author":"Sk\u0159i\u010dkov\u00e1 J.","year":"2018","journal-title":"Cas. Lek. Cesk."},{"key":"refg28\/ref28","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-023-02692-3"},{"key":"refg29\/ref29","doi-asserted-by":"publisher","DOI":"10.1111\/1759-7714.13328"},{"key":"refg30\/ref30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2003.10.006"},{"key":"refg31\/ref31","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22553"},{"key":"refg32\/ref32","doi-asserted-by":"publisher","DOI":"10.1038\/315239a0"},{"key":"refg33\/ref33","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S278233"},{"key":"refg34\/ref34","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14484"}],"container-title":["Biochemistry and Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdnsciencepub.com\/doi\/full-xml\/10.1139\/bcb-2025-0039","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdnsciencepub.com\/doi\/pdf\/10.1139\/bcb-2025-0039","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T15:28:22Z","timestamp":1762529302000},"score":1,"resource":{"primary":{"URL":"https:\/\/cdnsciencepub.com\/doi\/10.1139\/bcb-2025-0039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,1]]},"references-count":34,"alternative-id":["10.1139\/bcb-2025-0039"],"URL":"https:\/\/doi.org\/10.1139\/bcb-2025-0039","relation":{},"ISSN":["0829-8211","1208-6002"],"issn-type":[{"type":"print","value":"0829-8211"},{"type":"electronic","value":"1208-6002"}],"subject":[],"published":{"date-parts":[[2025,1,1]]},"assertion":[{"value":"2025-11-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}