NF-κB p65 subunit is modulated by latent transforming growth factor-β binding protein 2 (LTBP2) in nasopharyngeal carcinoma HONE1 and HK1 cells

Rebecca Kan, Wai Ho Shuen, Hong Lok Lung, Arthur Kwok Leung Cheung, Wei Dai, Dora Lai Wan Kwong, Wai Tong Ng, Anne Wing Mui Lee, Chun Chung Yau, Roger Kai Cheong Ngan, Stewart Yuk Tung, Maria Li Lung*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

32 Citations (Scopus)

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 micro-environment 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-βBinding 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.

Original languageEnglish
Article numbere0127239
Number of pages21
JournalPLoS ONE
Volume10
Issue number5
DOIs
Publication statusPublished - 14 May 2015
Externally publishedYes

Scopus Subject Areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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