title: Increase in IkappaB kinase alpha expression suppresses the tumor progression and improves the prognosis for nasopharyngeal carcinoma.
abstract: Recent studies have suggested that the action of IkappaB kinase alpha (IKKα) as a tumor suppressor is crucial in the development of skin carcinoma, but its role in nasopharyngeal carcinoma (NPC) remains unknown. We examined the IKKα expression in specimens from 157 NPC patients by immunohistochemistry and analyzed the effect of IKKα on prognosis. The functional significance of IKKα expression in NPC cell lines was investigated by IKKα overexpression or downregulation in in vitro studies. The in vitro assays revealed that the IKKα expression was negatively correlated with the invasiveness, migration, and angiogenesis of NPC cells. Overexpression or downregulation of IKKα could significantly repress or enhance the above characteristics, respectively, and these effects were independent of IKKα kinase or EBNA1. In 157 NPC cases, IKKα was differentially expressed in NPC tissues. High expression of IKKα was associated significantly with a high disease-free survival (DFS; P = 0.002) or overall survival (OS; P = 0.014). Multivariate analyses showed that the IKKα expression was an independent risk factor for DFS (HR, 2.302; P = 0.011) and OS (HR, 3.578; P = 0.006). Our findings indicated that IKKα plays a crucial role as a tumor suppressor that suppresses the invasion, metastasis, and angiogenesis of NPC cells in vitro and correlates with the survival in NPC patients. Therefore, IKKα is not only a novel independent prognostic indicator in NPC, but also targeting IKKα expression may provide a potential therapeutic strategy for NPC.
authors.affiliation: Department of Radiation Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Deng
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Ai
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Xie
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.forename: Nianyong
authors.initials: N
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics* / Q000378:metabolism*; D008207:Lymphatic Metastasis / Q000473:pathology* / Q000532:radiotherapy; D008297:Male; D008745:Methylation; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D016019:Survival Analysis
chemical_list: D051550:I-kappa B Kinase
keywords: IkappaB kinase alpha; nasopharyngeal carcinoma; prognostic marker; tumor malignant behaviors; tumor suppressor