title: Proteomic profiling between CNE-2 and its strongly metastatic subclone S-18 and functional characterization of HSP27 in metastasis of nasopharyngeal carcinoma.
abstract: Metastasis to secondary sites remains the leading cause of nasopharyngeal carcinoma (NPC)-associated death. In order to identify the candidate protein(s) responsible for the differential metastatic capacity, the protein expression profiling between NPC cell line CNE-2 and its highly metastatic subclone S-18 were compared by 2-DE. In total, 18 spots were differentially expressed between these two cell lines. Among all, seven proteins were identified with further MS analysis. Western blotting further validated upregulation of HSP27 and ezrin, and downregulation of valosin containing protein and keratin 18 in S-18. Moreover, the knockdown of HSP27 was found to significantly decrease the invasive ability of S-18. On the other hand, overexpression of HSP27 in NP460 cells, which generated little endogenous HSP27 and less invasive, was noted to gain enhanced metastatic capability. Real-time PCR confirmed that the transcriptional levels of NF-κB and MMP9, MMP11 were downregulated after inhibition of HSP27 in S-18, which implicated that HSP27 enhanced the metastatic property of NPC cells probably via the NF-κB-mediated activation of MMPs. The findings in this work provided us a platform for further elucidating the underlying mechanisms of NPC metastasis and demonstrated that HSP27 would be a valid target for anti-cancer drug development.
authors: Surgical Department of Head and Neck, The Third Affiliated Hospital, Kunming Medical University, Kunming, Yunnan, P. R. China.
authors: Guo-Ping
authors: GP
authors: Li
authors: Hua
authors: H
authors: Wang
authors: Yiu-Kay
authors: YK
authors: Lai
authors: Shao-Chun
authors: SC
authors: Chen
authors: Marie C M
authors: MC
authors: Lin
authors: Gang
authors: G
authors: Lu
authors: Jing-Fang
authors: JF
authors: Zhang
authors: Xiao-Guang
authors: XG
authors: He
authors: Chao-Nan
authors: CN
authors: Qian
authors: Hsiang-Fu
authors: HF
authors: Kung
mesh_terms: D002277:Carcinoma; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D055551:HSP27 Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000473:pathology*; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
chemical_list: D055551:HSP27 Heat-Shock Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D020543:Proteome; D034741:RNA, Small Interfering; D020782:Matrix Metalloproteinases