{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T14:55:35Z","timestamp":1777560935125,"version":"3.51.4"},"reference-count":47,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T00:00:00Z","timestamp":1668988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology, Taiwan","award":["MOST-106-2314-B-040-014"],"award-info":[{"award-number":["MOST-106-2314-B-040-014"]}]},{"name":"Ministry of Science and Technology, Taiwan","award":["CSH-2021-D-009"],"award-info":[{"award-number":["CSH-2021-D-009"]}]},{"DOI":"10.13039\/501100004699","name":"Chung Shan Medical University Hospital, Taiwan","doi-asserted-by":"publisher","award":["MOST-106-2314-B-040-014"],"award-info":[{"award-number":["MOST-106-2314-B-040-014"]}],"id":[{"id":"10.13039\/501100004699","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004699","name":"Chung Shan Medical University Hospital, Taiwan","doi-asserted-by":"publisher","award":["CSH-2021-D-009"],"award-info":[{"award-number":["CSH-2021-D-009"]}],"id":[{"id":"10.13039\/501100004699","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Nasopharyngeal carcinoma (NPC) is the most common cancer that occurs in the nasopharynx, and it is difficult to detect early. The main cause of death of NPC patients is cancer metastasis. Lipocalin 2 (LCN2) has been shown to be involved in a variety of carcinogenesis processes. Here, we aimed to study the role of LCN2 in NPC cells and determine its underlying mechanism. We found that LCN2 was expressed differently in NPC cell lines, namely HONE-1, NPC-39, and NPC-BM. The down-regulation of LCN2 levels by siRNA targeting LCN2 (siLCN2) increased cell migration and invasion in HONE-1 cells, while the up-regulation of LCN2 levels by transfection with the LCN2 expression plasmid decreased cell migration and invasion in NPC-BM cells. Furthermore, LCN2 levels negatively regulated the phosphorylation of MEK\/ERK pathways. The treatment of the specific MEK\/ERK inhibitor, U0126, reduced cell migration in HONE-1 cells, whereas the treatment of tBHQ, an ERK activator, enhanced cell migration in NPC-BM cells. Based on the bioinformatics data, there was a moderately negative correlation between LCN2 and MET in metastatic NPC tissues (r = \u22120.5946, p = 0.0022). Indeed, the manipulation of LCN2 levels negatively regulated MET levels in these NPC cells. The treatment of U0126 reduced siLCN2-increased MET levels, while the treatment of tBHQ enhanced LCN2-enhanced MET levels. Interestingly, the down-regulation of MET levels by siMET further decreased siLCN2-enhanced MET levels and cell migration. Therefore, LCN2 inhibits NPC cell migration by reducing MET levels through MEK\/ERK signaling.<\/jats:p>","DOI":"10.3390\/cancers14225707","type":"journal-article","created":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T03:13:41Z","timestamp":1669086821000},"page":"5707","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Lipocalin 2 Reduces MET Levels by Inhibiting MEK\/ERK Signaling to Inhibit Nasopharyngeal Carcinoma Cell Migration"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3406-4865","authenticated-orcid":false,"given":"Ju-Pi","family":"Li","sequence":"first","affiliation":[{"name":"School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"Department of Pediatrics, Chung Shan Medical University Hospital, Taichung 402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiao-Wen","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Oral Sciences, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"Department of Dentistry, Chung Shan Medical University Hospital, Taichung 402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng-Chen","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung 402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yen-Ting","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung 402, Taiwan"},{"name":"Department of Otolaryngology, St. Martin De Porres Hospital, Chiayi 600, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Ting","family":"Ho","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0365-7927","authenticated-orcid":false,"given":"Shun-Fa","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chung-Han","family":"Hsin","sequence":"additional","affiliation":[{"name":"School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung 402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1177\/014556130608500313","article-title":"Review of nasopharyngeal carcinoma","volume":"85","author":"Jeyakumar","year":"2006","journal-title":"Ear Nose Throat J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1158\/1055-9965.EPI-06-0353","article-title":"The enigmatic epidemiology of nasopharyngeal carcinoma","volume":"15","author":"Chang","year":"2006","journal-title":"Cancer Epidemiol. 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