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




Transducin β-like 1 X-linked receptor 1 suppresses cisplatin sensitivity in Nasopharyngeal Carcinoma via activation of NF-κB pathway - Download this document for free, or read online. Document in PDF available to download.

Molecular Cancer

, 13:195

First Online: 22 August 2014Received: 25 February 2014Accepted: 12 August 2014DOI: 10.1186-1476-4598-13-195

Cite this article as: Chen, SP., Yang, Q., Wang, CJ. et al. Mol Cancer 2014 13: 195. doi:10.1186-1476-4598-13-195

Abstract

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.

KeywordsTBL1XR1 Nasopharyngeal carcinoma Cisplatin Chemotherapy Anti-Apoptotic NF-κB signalling AbbreviationsTBL1XR1Transducin β-like 1 X-linked receptor 1

NPCNasopharyngeal carcinoma

IHCImmunohistochemical staining

TBLR1Transducin β-like-related protein 1

TBL1Transducin β-like protein 1

N-CoRNuclear receptor corepressor

SMRTSilencing mediator for retinoid and thyroid hormone receptors

PPARPeroxisome proliferator-activated receptor

CGHComparative genomic hybridization

shRNASmall hairpin RNA.

Electronic supplementary materialThe online version of this article doi:10.1186-1476-4598-13-195 contains supplementary material, which is available to authorized users.

Shu-Peng Chen, Qi Yang, Chan-Juan Wang contributed equally to this work.

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Author: Shu-Peng Chen - Qi Yang - Chan-Juan Wang - Long-Juan Zhang - Yi Fang - Fang-Yong Lei - Shu Wu - Li-Bing Song - Xiang Guo

Source: https://link.springer.com/







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