2015-05-14

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.

Kan, R, Shuen, WH, Lung, HL, Cheung, AKL, Dai, W, Kwong, DLW, Ng, WT, Lee, AWM, Yau, CC, Ngan, RKC, Tung, SY, Lung, ML. (2015). Data from: NF-κB p65 Subunit Is Modulated by Latent Transforming Growth Factor-β Binding Protein 2 (LTBP2) in Nasopharyngeal Carcinoma HONE1 and HK1 Cells. [Data File]. All relevant data are within the paper and its Supporting Information files. Click on “Linked Publications” to access the publication and access supporting information on figshare at https://figshare.com/articles/_NF_954_B_p65_Subunit_Is_Modulated_by_Latent_Transforming_Growth_Factor_946_Binding_Protein_2_LTBP2_in_Nasopharyngeal_Carcinoma_HONE1_and_HK1_Cells_/1415151

transforming

factor

binding

protein

Nasopharyngeal Carcinoma HONE 1

p 65

hk

propagating tumor growth

p 65 expression

nf

tumor suppressive effects

candidate ECM tumor suppressor

latent

NPC cells

candidate tumor suppressor

LTBP 2

p 65 transcriptional activity