Abstract
IκB kinase α (IKKα) is associated with tumourigenesis, metastasis, and poor prognosis.
However, its expression and function in oral squamous cell carcinoma (SCC) remain
unknown. The aim of this study was to elucidate the clinicopathological associations
and functions of IKKα in oral squamous cell carcinoma (SCC). We made an immunohistochemical
analysis of IKKα in 94 tissue microarrays of specimens of oral SCC. We also examined
IKKα expression in the patients’ samples by quantitative real-time polymerase chain
reaction (qRT-PCR), as well as the migration, invasion, and matrix metalloproteinase
(MMP) activity of the cells under IKKα knockdown treatment. In oral SCC, immunostaining
for IKKα was found in 60 of the 94 patients, and it correlated with lymph node status
and poor prognosis. Univariate and multivariate analysis using Cox’s proportional
hazards model identified that IKKα expression was an independent predictor of distant-
disease-free survival (p < 0.05) and overall survival in oral SCC (p < 0.05). Knocking down IKKα suppressed cell migration and invasion in oral SCC cells.
Our results indicate that IKKα has an important role in promoting oral SCC, and it
may be a useful biomarker and therapeutic target for diagnosis and treatment.
Keywords
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References
- Global cancer statistics, 2012.CA Cancer J Clin. 2015; 65: 87-108
- Cancer statistics, 2017.CA Cancer J Clin. 2017; 67: 7-30
- Roles of miR-138 and ISG15 in oral squamous cell carcinoma.Exp Ther Med. 2017; 14: 2329-2334
- HuD promotes progression of oral squamous cell carcinoma.Pathobiology. 2014; 81: 206-214
- IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation.Science. 1997; 278: 860-866
- IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK.Science. 1997; 278: 866-869
- The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation.Cell. 1997; 91: 243-252
- IkappaB kinase alpha functions as a tumor suppressor in epithelial-derived tumors through an NF-kappaB-independent pathway (Review).Oncol Rep. 2015; 34: 2225-2232
- IKKalpha is required to maintain skin homeostasis and prevent skin cancer.Cancer Cell. 2008; 14: 212-225
- The pivotal role of IKKalpha in the development of spontaneous lung squamous cell carcinomas.Cancer Cell. 2013; 23: 527-540
- Nuclear cytokine-activated IKKalpha controls prostate cancer metastasis by repressing Maspin.Nature. 2007; 446: 690-694
- Her2 activates NF-kappaB and induces invasion through the canonical pathway involving IKKalpha.Oncogene. 2010; 29: 1238-1248
- IKK(α) controls canonical TGF(β)-SMAD signaling to regulate genes expressing SNAIL and SLUG during EMT in panc1 cells.J Cell Sci. 2010; 123: 4231-4239
- High expression levels of nuclear factor kappaB, IkappaB kinase alpha and Akt kinase in squamous cell carcinoma of the oral cavity.Cancer. 2001; 92: 3037-3044
- Role of IKKalpha in skin squamous cell carcinomas.Future Oncol. 2011; 7: 123-134
- Increase in IkappaB kinase alpha expression suppresses the tumor progression and improves the prognosis for nasopharyngeal carcinoma.Mol Carcinog. 2015; 54: 156-165
- A nucleosomal function for IkappaB kinase-alpha in NF-kappaB-dependent gene expression.Nature. 2003; 423: 659-663
- Deciphering the role of nuclear and cytoplasmic IKKalpha in skin cancer.Oncotarget. 2016; 7: 29531-29547
- Cells lacking IKKalpha show nuclear cyclin D1 overexpression and a neoplastic phenotype: role of IKKalpha as a tumor suppressor.Mol Cancer Res. 2011; 9: 341-349
- High IKKalpha expression is associated with reduced time to recurrence and cancer specific survival in oestrogen receptor (ER)-positive breast cancer.Int J Cancer. 2017; 140: 1633-1644
- Predictive biomarkers for endocrine therapy: retrospective study in tamoxifen and exemestane adjuvant multinational (TEAM) trial.J Natl Cancer Inst. 2018; 110: 616-627
- miR-23a promotes IKKalpha expression but suppresses ST7L expression to contribute to the malignancy of epithelial ovarian cancer cells.Br J Cancer. 2016; 115: 731-740
- Blocking IKKalpha expression inhibits prostate cancer invasiveness.Pharm Res. 2011; 28: 1357-1369
- Noncanonical NF-kappaB activation requires coordinated assembly of a regulatory complex of the adaptors cIAP1, cIAP2, TRAF2 and TRAF3 and the kinase NIK.Nat Immunol. 2008; 9: 1371-1378
Article info
Publication history
Published online: December 19, 2019
Identification
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© 2019 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
