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Int. J. Mol. Sci. 2018, 19(2), 577; doi:10.3390/ijms19020577

Cytokeratin-8 in Anaplastic Thyroid Carcinoma: More Than a Simple Structural Cytoskeletal Protein

Departments of Otolaryngology Head/Neck Surgery, Augusta University, Augusta, GA 30912, USA
Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, GA 30912, USA
Departments of Otolaryngology, Molecular and Cellular Physiology, Feist-Weiller Cancer Center, LSU Health Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA
Proteomics Core Facility, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA
Departments of Pathology, Augusta University, Augusta, GA 30912, USA
Institute of Molecular and Cellular Biology, Department of Life Science, National Tsing Hua University, Hsinchu 300, Taiwan
Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
Division of Endocrinology and Metabolism, Mayo Clinic, Jacksonville, FL 32224, USA
Department of Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA
Author to whom correspondence should be addressed.
Received: 3 January 2018 / Revised: 25 January 2018 / Accepted: 8 February 2018 / Published: 14 February 2018
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [2480 KB, uploaded 14 February 2018]   |  


Anaplastic thyroid carcinoma (ATC) is almost universally fatal. Elevated keratin-8 (KRT8) protein expression is an established diagnostic cancer biomarker in several epithelial cancers (but not ATC). Several keratins, including KRT8, have been suggested to have a role in cell biology beyond that of structural cytoskeletal proteins. Here, we provide evidence that KRT8 plays a direct role in the growth of ATCs. Genomic and transcriptomic analysis of >5000 patients demonstrates that KRT8 mutation and copy number amplification are frequently evident in epithelial-derived cancers. Carcinomas arising from diverse tissues exhibit KRT8 mRNA and protein overexpression when compared to normal tissue levels. Similarly, in a panel of patient-derived ATC cell lines and patient tumors, KRT8 expression shows a similar pattern. sh-RNA-mediated KRT8 knockdown in these cell lines increases apoptosis, whereas forced overexpression of KRT8 confers resistance to apoptosis under peroxide-induced cell stress conditions. We further show that KRT8 protein binds to annexin A2, a protein known to mediate apoptosis as well as the redox pathway. View Full-Text
Keywords: cytokeratin-8; anaplastic thyroid carcinoma; apoptosis cytokeratin-8; anaplastic thyroid carcinoma; apoptosis

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Guo, D.; Xu, Q.; Pabla, S.; Koomen, J.; Biddinger, P.; Sharma, A.; Pabla, S.; Pacholczyk, R.; Chang, C.-C.; Friedrich, K.; Mohammed, K.; Smallridge, R.C.; Copland, J.A.; She, J.-X.; Weinberger, P.M. Cytokeratin-8 in Anaplastic Thyroid Carcinoma: More Than a Simple Structural Cytoskeletal Protein. Int. J. Mol. Sci. 2018, 19, 577.

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