NF-κB p65 Subunit Is Modulated by Latent Transforming Growth Factor-β Binding Protein 2 (LTBP2) in Nasopharyngeal Carcinoma HONE1 and HK1 Cells

PLoS One. 2015 May 14;10(5):e0127239. doi: 10.1371/journal.pone.0127239. eCollection 2015.

Abstract

NF-κB is a well-characterized transcription factor, widely known as a key player in tumor-derived inflammation and cancer development. Herein, we present the functional and molecular relevance of the canonical NF-κB p65 subunit in nasopharyngeal carcinoma (NPC). Loss- and gain-of-function approaches were utilized to reveal the functional characteristics of p65 in propagating tumor growth, tumor-associated angiogenesis, and epithelial-to-mesenchymal transition in NPC cells. Extracellular inflammatory stimuli are critical factors that trigger the NF-κB p65 signaling; hence, we investigated the components of the tumor microenvironment that might potentially influence the p65 signaling pathway. This led to the identification of an extracellular matrix (ECM) protein that was previously reported as a candidate tumor suppressor in NPC. Our studies on the Latent Transforming Growth Factor-β Binding Protein 2 (LTBP2) protein provides substantial evidence that it can modulate the p65 transcriptional activity. Re-expression of LTBP2 elicits tumor suppressive effects that parallel the inactivation of p65 in NPC cells. LTBP2 was able to reduce phosphorylation of p65 at Serine 536, inhibit nuclear localization of active phosphorylated p65, and impair the p65 DNA-binding ability. This results in a consequential down-regulation of p65-related gene expression. Therefore, the data suggest that the overall up-regulation of p65 expression and the loss of this candidate ECM tumor suppressor are milestone events contributing to NPC development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Latent TGF-beta Binding Proteins / metabolism*
  • NF-kappa B / metabolism*
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / pathology
  • Phosphorylation
  • Signal Transduction
  • Transcription Factor RelA / metabolism*
  • Tumor Microenvironment

Substances

  • LTBP2 protein, human
  • Latent TGF-beta Binding Proteins
  • NF-kappa B
  • Transcription Factor RelA

Grants and funding

This work was supported by Hong Kong Research Grants Council grant, AoE/M-06/08. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.