Abstract
The NAG7, an estrogen receptor repressor, is a negative regulator of nasopharyngeal carcinoma cell growth. Here, we report that NAG7 promotes human nasopharyngeal carcinoma invasion, and we identify the mechanisms underlying this function. As a consequence of elevated NAG7 expression, the adhesion, migration, and invasive capabilities of HNE1 cells in vitro and in vivo were enhanced. NAG7 was a significant negative regulator of protein expression of estrogen receptor alpha (ERalpha), and activated both the JNK2/AP-1/MMP1 and the upstream H-Ras/p-c-Raf pathways. None of these effects induced by NAG7 over-expression could be counteracted by estrogen. These observations indicate that NAG7 plays a potential role in promoting nasopharyngeal carcinoma invasion by regulation of ERalpha and the H-ras/p-c-Raf and JNK2/AP-1/MMP1 signaling pathways.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cell Line, Tumor
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Estradiol / pharmacology
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Estrogen Receptor alpha / antagonists & inhibitors*
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Estrogen Receptor alpha / metabolism
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Matrix Metalloproteinase 1 / metabolism
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Mitogen-Activated Protein Kinase 9 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 9 / metabolism
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Nasopharyngeal Neoplasms / enzymology*
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Nasopharyngeal Neoplasms / genetics
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Nasopharyngeal Neoplasms / pathology*
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Neoplasm Invasiveness / pathology*
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Protein Kinase Inhibitors / pharmacology
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Proto-Oncogene Proteins c-raf / metabolism
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Proto-Oncogene Proteins p21(ras) / metabolism
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RNA, Long Noncoding
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RNA, Untranslated
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Signal Transduction* / drug effects
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Transcription Factor AP-1 / metabolism
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
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Up-Regulation* / drug effects
Substances
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Cell Cycle Proteins
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Estrogen Receptor alpha
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LINC00312 long non-coding RNA, human
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Membrane Proteins
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Protein Kinase Inhibitors
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RNA, Long Noncoding
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RNA, Untranslated
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Transcription Factor AP-1
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Tumor Suppressor Proteins
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Estradiol
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Mitogen-Activated Protein Kinase 9
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Proto-Oncogene Proteins c-raf
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Matrix Metalloproteinase 1
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HRAS protein, human
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Proto-Oncogene Proteins p21(ras)