Next Article in Journal
Charged N-terminus of Influenza Fusion Peptide Facilitates Membrane Fusion
Previous Article in Journal
Proteomic Differences in Feline Fibrosarcomas Grown Using Doxorubicin-Sensitive and -Resistant Cell Lines in the Chick Embryo Model
Article Menu
Issue 2 (February) cover image

Export Article

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

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

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 xuqzju@gmail.com
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.
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]   |  

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
Figures

Figure 1a

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).

Supplementary material

SciFeed

Share & Cite This Article

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top