Cytokeratin-8 in anaplastic thyroid carcinoma: More than a simple structural cytoskeletal protein

Dehuang Guo, Qinqin Xu, Sarabjot Pabla, John Koomen, Paul Williams Biddinger, Ashok Kumar Sharma, Simarjot Pabla, Rafal W Pacholczyk, Chien Chung Chang, Kevin Friedrich, Kamran Mohammed, Robert C. Smallridge, John A. Copland, Jin-Xiong She, Paul M. Weinberger

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish (US)
Article number577
JournalInternational journal of molecular sciences
Volume19
Issue number2
DOIs
StatePublished - Feb 14 2018

Keywords

  • Anaplastic thyroid carcinoma
  • Apoptosis
  • Cytokeratin-8

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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  • Cite this

    Guo, D., Xu, Q., Pabla, S., Koomen, J., Biddinger, P. W., Sharma, A. K., Pabla, S., Pacholczyk, R. W., Chang, C. C., Friedrich, K., Mohammed, K., Smallridge, R. C., Copland, J. A., She, J-X., & Weinberger, P. M. (2018). Cytokeratin-8 in anaplastic thyroid carcinoma: More than a simple structural cytoskeletal protein. International journal of molecular sciences, 19(2), [577]. https://doi.org/10.3390/ijms19020577