中山醫學大學機構典藏 CSMUIR:Item 310902500/23893
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    題名: CCL4 Stimulates Cell Migration in Human Osteosarcoma via the mir-3927-3p/Integrin alpha v beta 3 Axis
    作者: Tsai, HC;Lai, YY;Hsu, HC;Fong, YC;Lien, MY;Tang, CH
    關鍵詞: CCL4;integrin;miR-3927-3p;metastasis;osteosarcoma
    日期: 2021
    上傳時間: 2022-08-05T09:44:34Z (UTC)
    出版者: MDPI
    摘要: Osteosarcoma is the most common type of primary malignant bone cancer, and it is associated with high rates of pulmonary metastasis. Integrin alpha v beta 3 is critical for osteosarcoma cell migratory and invasive abilities. Chemokine (C-C motif) ligand 4 (CCL4) has diverse effects on different cancer cells through its interaction with its specific receptor, C-C chemokine receptor type 5 (CCR5). Analysis of mRNA expression in human osteosarcoma tissue identified upregulated levels of CCL4, integrin alpha v and beta 3 expression. Similarly, an analysis of records from the Gene Expression Omnibus (GEO) dataset showed that CCL4 was upregulated in human osteosarcoma tissue. Importantly, the expression of both CCL4 and integrin alpha v beta 3 correlated positively with osteosarcoma clinical stages and lung metastasis. Analysis of osteosarcoma cell lines identified that CCL4 promotes integrin alpha v beta 3 expression and cell migration by activating the focal adhesion kinase (FAK), protein kinase B (AKT), and hypoxia inducible factor 1 subunit alpha (HIF-1 alpha) signaling pathways, which can downregulate microRNA-3927-3p expression. Pharmacological inhibition of CCR5 by maraviroc (MVC) prevented increases in integrin alpha v beta 3 expression and cell migration. This study is the first to implicate CCL4 as a potential target in the treatment of metastatic osteosarcoma.
    URI: http://dx.doi.org/10.3390/ijms222312737
    https://www.webofscience.com/wos/woscc/full-record/WOS:000735174400001
    https://ir.csmu.edu.tw:8080/handle/310902500/23893
    關聯: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES ,2021,v22,issue 23
    顯示於類別:[中山醫學大學研究成果] 期刊論文

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