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 journalArticlepeer-review

4 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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