中山醫學大學機構典藏 CSMUIR:Item 310902500/23803
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    题名: Lipocalin-2 Inhibits Osteosarcoma Cell Metastasis by Suppressing MET Expression via the MEK-ERK Pathway
    作者: Lu, KH;Yang, JS;Hsieh, YH;Chu, HJ;Chou, CH;Lu, EWH;Lin, CW;Yang, SF
    关键词: LCN2;metastasis;osteosarcoma;MET
    日期: 2021
    上传时间: 2022-08-05T09:43:07Z (UTC)
    出版者: MDPI
    摘要: Simple Summary Higher neutrophil-derived cytokine lipocalin-2 (LCN2) expression possesses a versatile role in a myriad of cancers, but little is known about the role of LCN2 on osteosarcoma metastasis. In this study, we demonstrated that higher LCN2 inhibited cellular motility, migration, and invasion of osteosarcoma cells. Moreover, the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was decreased by LCN2 knockdown. Conclusively, LCN2 inhibits osteosarcoma cell metastasis by suppressing MET via the mitogen-activated protein kinases/ERK kinase (MEK)-ERK pathway. Higher neutrophil-derived cytokine lipocalin-2 (LCN2) expression possesses a versatile role in a myriad of cancers, but little is known about the role of LCN2 on osteosarcoma metastasis. In this study, we demonstrated that higher LCN2 inhibited cellular motility, migration, and invasion of osteosarcoma cells. Moreover, using RNA sequencing technology, we found that LCN2 repressed MET gene expression in U2OS cells. Manipulation of LCN2 levels influenced the migratory potential of osteosarcoma cells as cellular migration was enhanced by transfecting with vectors containing a constitutively active LCN2 cDNA and recombinant human LCN2. Moreover, the phosphorylation of mitogen-activated protein kinases/extracellular signal-regulated kinase (ERK) kinase (MEK) 1/2 and ERK 1/2 was decreased by LCN2 knockdown. Furthermore, the use of ERK inhibitor (U0126) and activator (tBHQ) confirmed that the pharmaceutic inhibition of MEK-ERK augmented the LCN2-mediated MET suppression and migration of U2OS and HOS cells. Conclusively, LCN2 inhibits osteosarcoma cell metastasis by suppressing MET via the MEK-ERK pathway.
    URI: http://dx.doi.org/10.3390/cancers13133181
    https://www.webofscience.com/wos/woscc/full-record/WOS:000671102400001
    https://ir.csmu.edu.tw:8080/handle/310902500/23803
    關聯: CANCERS ,2021,v13,issue 13
    显示于类别:[中山醫學大學研究成果] 期刊論文

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