{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T11:45:39Z","timestamp":1785843939932,"version":"3.56.0"},"reference-count":40,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073061"],"award-info":[{"award-number":["82073061"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014761","name":"Natural Science Foundation of Qingdao Municipality","doi-asserted-by":"publisher","award":["24\u20104\u20104\u2010zrjj\u2010160\u2010jch"],"award-info":[{"award-number":["24\u20104\u20104\u2010zrjj\u2010160\u2010jch"]}],"id":[{"id":"10.13039\/501100014761","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Metastasis is the leading cause of death in patients with colon cancer. Although Lemur tyrosine kinase 2 (LMTK2) has been implicated in cell proliferation, its role in metastasis is unclear. In this study, we found that low\n                    <jats:italic>LMTK2<\/jats:italic>\n                    expression correlates with metastatic status (M1 stage) and a higher metastasis rate in a large colon cancer cohort. Additionally,\n                    <jats:italic>LMTK2<\/jats:italic>\n                    expression is negatively correlated with pro\u2010metastatic genes and positively correlated with metastasis suppressors, a pattern that was validated in 50 clinical colon cancer specimens. Functional studies demonstrated that LMTK2 potently inhibits cell migration and invasion in\u00a0vitro and suppresses metastasis in a mouse model in\u00a0vivo. Mechanistically, LMTK2 disrupts the interaction between p38 MAPK and its upstream kinases MKK3\/6, thereby inhibiting p38 activation and subsequent cell migration and invasion. Notably, the kinase\u2010deficient LMTK2 (K168R) mutant also suppresses p38 phosphorylation and impedes cell migration and invasion. These results uncover a novel anti\u2010metastatic function of LMTK2, which acts through inhibition of p38 independently of its kinase activity.\n                  <\/jats:p>","DOI":"10.1111\/cas.70490","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T11:09:46Z","timestamp":1785841786000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>LMTK2<\/scp>\n                    Inhibits Metastasis of Colon Cancer Cells Through p38\n                    <scp>MAPK<\/scp>"],"prefix":"10.1111","author":[{"given":"Jie","family":"Lun","sequence":"first","affiliation":[{"name":"Department of Oncology The Affiliated Hospital of Qingdao University, Qingdao Cancer Institute  Qingdao China"},{"name":"School of Pharmacy Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute for Nutrition and Health Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Oncology The Affiliated Hospital of Qingdao University, Qingdao Cancer Institute  Qingdao China"},{"name":"School of Pharmacy Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyuan","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Oncology The Affiliated Hospital of Qingdao University, Qingdao Cancer Institute  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqing","family":"Qin","sequence":"additional","affiliation":[{"name":"Institute for Nutrition and Health Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Oncology The Affiliated Hospital of Qingdao University, Qingdao Cancer Institute  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0183-1654","authenticated-orcid":false,"given":"Mengchao","family":"Yu","sequence":"additional","affiliation":[{"name":"Central Laboratory Qingdao Municipal Hospital  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"issue":"1","key":"e_1_2_12_2_1","first-page":"10","article-title":"Cancer Statistics, 2025","volume":"75","author":"Siegel R. 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V.","year":"2007","journal-title":"Journal of Cell Science"},{"issue":"5","key":"e_1_2_12_8_1","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/j.1365-2443.2008.01184.x","article-title":"BREK\/LMTK2 Is a Myosin VI\u2010Binding Protein Involved in Endosomal Membrane Trafficking","volume":"13","author":"Inoue T.","year":"2008","journal-title":"Genes to Cells"},{"issue":"3","key":"e_1_2_12_9_1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/j.1356-9597.2004.00714.x","article-title":"Involvement of BREK, a Serine\/Threonine Kinase Enriched in Brain, in NGF Signalling","volume":"9","author":"Kawa S.","year":"2004","journal-title":"Genes to Cells"},{"issue":"4","key":"e_1_2_12_10_1","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.bbrc.2019.11.002","article-title":"Overexpression of Lemur Tyrosine Kinase\u20102 Protects Neurons From Oxygen\u2010Glucose Deprivation\/Reoxygenation\u2010Induced Injury Through Reinforcement of Nrf2 Signaling by Modulating GSK\u20103beta Phosphorylation","volume":"521","author":"Bao H.","year":"2020","journal-title":"Biochemical and Biophysical Research Communications"},{"issue":"5","key":"e_1_2_12_11_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.tjpad.2025.100087","article-title":"LMTK2 and CRB1 Are Two Novel Risk Genes for Alzheimer's Disease in Han Chinese","volume":"12","author":"Xiao X.","year":"2025","journal-title":"Journal of Prevention of Alzheimer's Disease"},{"issue":"1","key":"e_1_2_12_12_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s40478-019-0715-5","article-title":"LMTK2 Binds to Kinesin Light Chains to Mediate Anterograde Axonal Transport of cdk5\/p35 and LMTK2 Levels Are Reduced in Alzheimer's Disease Brains","volume":"7","author":"Morotz G. 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