NAG7 promotes human nasopharyngeal carcinoma invasion through inhibition of estrogen receptor alpha and up-regulation of JNK2/AP-1/MMP1 pathways.
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.
Huang
Chen
C
Cancer Research Institute, Central South University, Changsha, Hunan, PR China.
Wu
Minghua
M
Tang
Yunlian
Y
Li
Xiaoling
X
Ouyang
Jue
J
Xiao
Lan
L
Li
Dan
D
Li
Guiyuan
G
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D048056:Mitogen-Activated Protein Kinase 9 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D018797:Cell Cycle Proteins; D047628:Estrogen Receptor alpha; C470228:LINC00312 long non-coding RNA, human; D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D018808:Transcription Factor AP-1; D025521:Tumor Suppressor Proteins; D004958:Estradiol; D048056:Mitogen-Activated Protein Kinase 9; D019908:Proto-Oncogene Proteins c-raf; D020781:Matrix Metalloproteinase 1; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)