Transducin β-like 1 X-linked receptor 1 suppresses cisplatin sensitivity in Nasopharyngeal Carcinoma via activation of NF-κB pathway

Molecular Cancer

Research

Shu-Peng Chen¹  Fang-Yong Lei¹  Shu Wu¹  Li-Bing Song¹  Chan-Juan Wang²  Ling Guo³  Xiang Guo³  Qi Yang³  Yi Fang⁴  Long-Juan Zhang⁵ 

[1] Department of Experimental Research, State Key Laboratory of Oncology in South China Guangzhou, 510060, Guangdong, People’s Republic of China;Department of Experimental Research, State Key Laboratory of Oncology in South China Guangzhou, 510060, Guangdong, People’s Republic of China;Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in South China Guangzhou, 510060, Guangdong, People’s Republic of China;Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in South China Guangzhou, 510060, Guangdong, People’s Republic of China;Department of Pulmonary Function Laboratory, Intensive Care Unit, State Key Laboratory of Oncology in South China Guangzhou, 510060, Guangdong, People’s Republic of China;Laboratory of General Surgery, The First Affiliated Hospital of Sun Yat-sen University Guangzhou, 510080, Guangdong, People’s Republic of China;

关键词: TBL1XR1;    Nasopharyngeal carcinoma;    Cisplatin;    Chemotherapy;    Anti-Apoptotic;    NF-κB signalling;   

DOI  :  10.1186/1476-4598-13-195

 received in 2014-02-25, accepted in 2014-08-12,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundTransducin 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.MethodsWe 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.ResultsTBL1XR1 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.ConclusionsUpregulation 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.

【 授权许可】

Unknown   
© Chen et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.