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

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...

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Published in:International journal of molecular sciences 2018-02, Vol.19 (2), p.577
Main Authors: Guo, Dehuang, Xu, Qinqin, Pabla, Sarabjot, Koomen, John, Biddinger, Paul, Sharma, Ashok, Pabla, Simarjot, Pacholczyk, Rafal, Chang, Chien-Chung, Friedrich, Kevin, Mohammed, Kamran, Smallridge, Robert C, Copland, John A, She, Jin-Xiong, Weinberger, Paul M
Format: Article
Language:English
Subjects:
anaplastic thyroid carcinoma
Apoptosis
Carcinoma
Cellular stress response
Copy number
Cytokeratin
cytokeratin-8
Cytoskeleton
Diagnostic systems
Gene expression
Keratin
Peroxide
Proteins
Thyroid cancer
Thyroid carcinoma
Tumors
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Summary: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 mutation and copy number amplification are frequently evident in epithelial-derived cancers. Carcinomas arising from diverse tissues exhibit 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 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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms19020577