Oncotarget

Research Papers:

Caspase 12 degrades IκBα protein and enhances MMP-9 expression in human nasopharyngeal carcinoma cell invasion

Wing-Keung Chu, Chih-Chin Hsu, Shiang-Fu Huang, Chia-Chi Hsu and Shu-Er Chow _

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Oncotarget. 2017; 8:33515-33526. https://doi.org/10.18632/oncotarget.16535

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Abstract

Wing-Keung Chu1,2, Chih-Chin Hsu3,4, Shiang-Fu Huang5, Chia-Chi Hsu6 and Shu-Er Chow5,6

1Department of Physiology, Chang Gung University, Taoyuan, Taiwan

2Center for Healthy and Aging Research, College of Medicine, Chang Gung University, Taoyuan, Taiwan

3Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital at Keelung, Keelung, Taiwan

4Department of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan

5Department of Otolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan

6Department of Nature Science, Center for General Studies, Chang Gung University, Taoyuan, Taiwan

Correspondence to:

Shu-Er Chow, email: chowse@mail.cgu.edu.tw

Keywords: Caspase-12, cell invasion, IκBα, NF-κB, human nasopharyngeal carcinoma

Received: December 07, 2016    Accepted: March 03, 2017    Published: March 23, 2017

ABSTRACT

Caspase-12 (Casp12), an inflammatory caspase, functions as a dominant-negative regulator of inflammatory responses and is associated with the signaling of apoptosis. However, the physiological function of Casp12 presented in cancer cells is still unclear. This study demonstrated that overexpression of Casp12 mediated IκBα degradation and significantly increased NF-κB activity. Exposure of human nasopharyngeal carcinoma (NPC) cells to phorbol-12-myristate-13-acetate (PMA) increased the levels of Casp12 and MMP-9 resulting in NPC cell invasion. Target suppression of Casp12 by small interfering RNA (siRNA) or an inhibitor of Casp12 markedly decreased the level of PMA-induced MMP-9 protein and cell invasion. Moreover, suppression of Casp12 significantly inhibited the basal activity of NF-κB and decreased the PMA-induced NF-κB reporter activity. The effect of Casp12 on NF-κB activation was indicated via the post-translational degradation of IκB. This study revealed that a critical role of Casp12 on the activation of NF-κB via IκBα degradation which provides a link between inflammatory and aggressive invasion in NPC cells.


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