title: Transducin β-like 1 X-linked receptor 1 suppresses cisplatin sensitivity in nasopharyngeal carcinoma via activation of NF-κB pathway.
abstract: BACKGROUND
  Transducin β-like 1 X-linked receptor 1 (TBL1XR1) is an important transcriptional cofactor involved in the regulation of many signaling pathways, and is associated with carcinogenesis and tumor progression. However, the precise role of TBL1XR1 in these processes is not well understood.
  
  
  METHODS
  We detected the expression of TBL1XR1 protein and mRNA in nasopharyngeal carcinoma (NPC) cell lines and biopsies by western blotting, real-time PCR and immunohistochemical staining (IHC). Overexpression of TBL1XR1 in NPC enhanced chemoresistance to cisplatin using two NPC cell lines in vitro and in vivo.
  
  
  RESULTS
  TBL1XR1 was upregulated in NPC cell lines and clinical samples. The expression of TBL1XR1 was correlated with several clinicopathological factors including clinical stage, T classification, N classification and patient survival. Univariate and multivariate analysis revealed that TBL1XR1 was an independent prognostic factor for patient survival. In vitro and in vivo studies demonstrated that TBL1XR1 high expression induced resistance to cisplatin-induced apoptosis in NPC cells. Furthermore, we found that TBL1XR1 activated the NF-κB pathway and promoted transcription of genes downstream of NF-κB, especially anti-apoptotic genes.
  
  
  CONCLUSIONS
  Upregulation of TBL1XR1 induces NPC cells resistance to cisplatin by activating the NF-κB pathway, and correlates with poor overall survival of NPC patients. TBL1XR1 has a pivotal role in NPC and could be a valuable prognostic factor as well as a novel biomarker for tailoring appropriate therapeutic regimes.
authors.forename: Shu-Peng
authors.initials: SP
authors.lastname: Chen
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.forename: Chan-Juan
authors.initials: CJ
authors.lastname: Wang
authors.forename: Long-Juan
authors.initials: LJ
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Fang
authors.forename: Fang-Yong
authors.initials: FY
authors.lastname: Lei
authors.forename: Shu
authors.initials: S
authors.lastname: Wu
authors.forename: Li-Bing
authors.initials: LB
authors.lastname: Song
authors.affiliation: Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in South China Guangzhou, Guangdong 510060, People's Republic of China. guoxiang@sysucc.org.cn.
authors.forename: Xiang
authors.initials: X
authors.lastname: Guo
authors.forename: Ling
authors.initials: L
authors.lastname: Guo
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002277:Carcinoma; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology*; D009374:Neoplasms, Experimental; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016019:Survival Analysis
chemical_list: D016328:NF-kappa B; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; C473691:TBL1XR1 protein, human; D002945:Cisplatin