Transducin β-like 1 X-linked receptor 1 suppresses cisplatin sensitivity in nasopharyngeal carcinoma via activation

Shu-Peng Chen, Qi Yang, Chan-Juan Wang

  • 1Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in South China Guangzhou, Guangdong 510060, People's Republic of China. guoxiang@sysucc.org.cn.

Molecular Cancer
|August 23, 2014
PubMed
Abstract

Insights

Transducin β-like 1 X-linked receptor 1 (TBL1XR1) upregulation in nasopharyngeal carcinoma (NPC) promotes cisplatin resistance by activating the NF-κB pathway. This finding suggests TBL1XR1 is a prognostic factor and potential therapeutic target for NPC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Transducin β-like 1 X-linked receptor 1 (TBL1XR1) is a transcriptional cofactor implicated in various signaling pathways and cancer.
  • Its specific role in carcinogenesis and tumor progression, particularly in nasopharyngeal carcinoma (NPC), remains unclear.

Purpose of the Study:

  • To investigate the role of TBL1XR1 in nasopharyngeal carcinoma (NPC).
  • To determine the association between TBL1XR1 expression and chemoresistance to cisplatin.
  • To explore TBL1XR1 as a prognostic marker in NPC.

Main Methods:

  • TBL1XR1 protein and mRNA expression were analyzed in NPC cell lines and patient biopsies using western blotting, real-time PCR, and immunohistochemistry.
  • Chemoresistance to cisplatin was assessed in NPC cell lines in vitro and in vivo following TBL1XR1 overexpression.
  • The NF-κB signaling pathway activation was investigated in relation to TBL1XR1 expression.

Main Results:

  • TBL1XR1 was found to be upregulated in NPC cell lines and clinical samples.
  • High TBL1XR1 expression correlated with advanced clinical stage, T classification, N classification, and poorer patient survival.
  • Overexpression of TBL1XR1 conferred resistance to cisplatin-induced apoptosis in NPC cells, mediated by activation of the NF-κB pathway and increased transcription of anti-apoptotic genes.

Conclusions:

  • Upregulated TBL1XR1 contributes to cisplatin resistance in NPC by activating the NF-κB pathway.
  • TBL1XR1 expression is a significant independent prognostic factor for overall survival in NPC patients.
  • TBL1XR1 represents a potential therapeutic target and biomarker for personalized treatment strategies in NPC.

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