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Volume 19
Issue 2
10.3390/ijms19020577
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Article

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

by
Dehuang Guo
1,2,
Qinqin Xu
3,
Sarabjot Pabla
2,
John Koomen
4,
Paul Biddinger
5,
Ashok Sharma
2,
Simarjot Pabla
2,
Rafal Pacholczyk
2,
Chien-Chung Chang
6,
Kevin Friedrich
7,
Kamran Mohammed
1,
Robert C. Smallridge
8,9,
John A. Copland
9,
Jin-Xiong She
2 and
Paul M. Weinberger
3,*
1
Departments of Otolaryngology Head/Neck Surgery, Augusta University, Augusta, GA 30912, USA
2
Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, GA 30912, USA
3
Departments of Otolaryngology, Molecular and Cellular Physiology, Feist-Weiller Cancer Center, LSU Health Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA [email protected]
4
Proteomics Core Facility, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA
5
Departments of Pathology, Augusta University, Augusta, GA 30912, USA
6
Institute of Molecular and Cellular Biology, Department of Life Science, National Tsing Hua University, Hsinchu 300, Taiwan
7
Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
8
Division of Endocrinology and Metabolism, Mayo Clinic, Jacksonville, FL 32224, USA
9
Department of Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(2), 577; https://doi.org/10.3390/ijms19020577
Received: 3 January 2018 / Revised: 25 January 2018 / Accepted: 8 February 2018 / Published: 14 February 2018
(This article belongs to the Section Biochemistry)
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Abstract

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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MDPI and ACS Style

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. https://doi.org/10.3390/ijms19020577

AMA Style

Guo D, Xu Q, Pabla S, Koomen J, Biddinger P, Sharma A, Pabla S, Pacholczyk R, Chang C-C, Friedrich K, Mohammed K, Smallridge RC, Copland JA, She J-X, Weinberger PM. Cytokeratin-8 in Anaplastic Thyroid Carcinoma: More Than a Simple Structural Cytoskeletal Protein. International Journal of Molecular Sciences. 2018; 19(2):577. https://doi.org/10.3390/ijms19020577

Chicago/Turabian Style

Guo, Dehuang, Qinqin Xu, Sarabjot Pabla, John Koomen, Paul Biddinger, Ashok Sharma, Simarjot Pabla, Rafal Pacholczyk, Chien-Chung Chang, Kevin Friedrich, Kamran Mohammed, Robert C. Smallridge, John A. Copland, Jin-Xiong She, and Paul M. Weinberger. 2018. "Cytokeratin-8 in Anaplastic Thyroid Carcinoma: More Than a Simple Structural Cytoskeletal Protein" International Journal of Molecular Sciences 19, no. 2: 577. https://doi.org/10.3390/ijms19020577

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