Melatonin suppresses TPA‐induced metastasis by downregulating matrix metalloproteinase‐9 expression through JNK/SP‐1 signaling in nasopharyngeal carcinoma

doi:10.1111/jpi.12365

中山醫學大學機構典藏 CSMUIR > 口腔醫學院 > 口腔醫學研究所 > 期刊論文 > Item 310902500/19409

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题名:	Melatonin suppresses TPA‐induced metastasis by downregulating matrix metalloproteinase‐9 expression through JNK/SP‐1 signaling in nasopharyngeal carcinoma
作者:	Ho, Hsin‐Yu;Lin, Chiao‐Wen;Chien, Ming‐Hsien;Reiter, Russel J.;Su, Shih‐Chi;Hsieh, Yi‐Hsien;Yang, Shun‐Fa
贡献者:	中山醫學大學口腔醫學研究所
关键词:	melatonin;metastasis;MMP;nasopharyngeal carcinoma;SP‐1
日期:	2016-09-07
上传时间:	2018-10-17T08:00:59Z (UTC)
摘要:	Nasopharyngeal carcinoma (NPC), a disease common in the South‐East Asian population, has high lymph node metastatic ability. Melatonin, an endogenously produced substance present in animals, plants, fungi, and bacteria, has oncostatic activity via several mechanisms. The molecular mechanisms involved in melatonin‐mediated tumor inhibitory potential are not completely defined. Here, we show that melatonin treatment inhibits TPA‐induced cell motility by regulating the matrix metalloproteinase‐9 (MMP‐9) expression in NPC. We also identified the signaling cascade through which melatonin inhibits MMP‐9 expression; this involves melatonin regulating the binding activity of the transcription factor specificity protein‐1 (SP‐1)‐DNA. Our mechanistic analysis further reveals that the c‐Jun N‐terminal kinase/mitogen‐activated protein kinase pathway is involved in the melatonin‐mediated tumor suppressor activity. Furthermore, the findings indicate a functional link between melatonin‐mediated MMP‐9 regulation and tumor suppressing ability and provide new insights into the role of melatonin‐induced molecular and epigenetic regulation of tumor growth. Thus, we conclude that melatonin suppresses the motility of NPC by regulating TPA‐induced MMP‐9 gene expression via inhibiting SP‐1‐DNA binding ability. The results provide a functional link between melatonin‐mediated SP‐1 regulation and the antimetastatic actions of melatonin on nasopharyngeal carcinoma.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/19409
關聯:	Journal of Pineal Research, vol.61, issue 4,479-492
显示于类别:	[口腔醫學研究所] 期刊論文

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