title: Caspase 12 degrades IκBα protein and enhances MMP-9 expression in human nasopharyngeal carcinoma cell invasion.
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.
authors.affiliation: Department of Physiology, Chang Gung University, Taoyuan, Taiwan.|Center for Healthy and Aging Research, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Wing-Keung
authors.initials: WK
authors.lastname: Chu
authors.affiliation: Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital at Keelung, Keelung, Taiwan.|Department of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chih-Chin
authors.initials: CC
authors.lastname: Hsu
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Shiang-Fu
authors.initials: SF
authors.lastname: Huang
authors.affiliation: Department of Nature Science, Center for General Studies, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Hsu
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|Department of Nature Science, Center for General Studies, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Shu-Er
authors.initials: SE
authors.lastname: Chow
mesh_terms: D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D053454:Caspase 12 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D059748:Proteolysis; D034622:RNA Interference
chemical_list: D020672:I-kappa B Proteins; D000072000:NF-KappaB Inhibitor alpha; D053454:Caspase 12; D020780:Matrix Metalloproteinase 9
keywords: Caspase-12; IκBα; NF-κB; cell invasion; human nasopharyngeal carcinoma