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 Citations (Scopus)

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

Fingerprint

Keratin-8
keratins
Keratin
Cytoskeletal Proteins
cancer
proteins
Proteins
apoptosis
Cell death
Apoptosis
cultured cells
Cells
Annexin A2
Cytology
Tissue
Anaplastic Thyroid Carcinoma
Peroxides
Tumor Biomarkers
Keratins
biomarkers

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

Cite this

Cytokeratin-8 in anaplastic thyroid carcinoma : More than a simple structural cytoskeletal protein. / Guo, Dehuang; Xu, Qinqin; Pabla, Sarabjot; Koomen, John; Biddinger, Paul Williams; Sharma, Ashok Kumar; Pabla, Simarjot; Pacholczyk, Rafal W; Chang, Chien Chung; Friedrich, Kevin; Mohammed, Kamran; Smallridge, Robert C.; Copland, John A.; She, Jin-Xiong; Weinberger, Paul M.

In: International journal of molecular sciences, Vol. 19, No. 2, 577, 14.02.2018.

Research output: Contribution to journalArticle

Guo, D, Xu, Q, Pabla, S, Koomen, J, Biddinger, PW, Sharma, AK, Pabla, S, Pacholczyk, RW, Chang, CC, Friedrich, K, Mohammed, K, Smallridge, RC, Copland, JA, She, J-X & Weinberger, PM 2018, 'Cytokeratin-8 in anaplastic thyroid carcinoma: More than a simple structural cytoskeletal protein', International journal of molecular sciences, vol. 19, no. 2, 577. https://doi.org/10.3390/ijms19020577
Guo, Dehuang ; Xu, Qinqin ; Pabla, Sarabjot ; Koomen, John ; Biddinger, Paul Williams ; Sharma, Ashok Kumar ; Pabla, Simarjot ; Pacholczyk, Rafal W ; Chang, Chien Chung ; Friedrich, Kevin ; Mohammed, Kamran ; Smallridge, Robert C. ; Copland, John A. ; She, Jin-Xiong ; Weinberger, Paul M. / Cytokeratin-8 in anaplastic thyroid carcinoma : More than a simple structural cytoskeletal protein. In: International journal of molecular sciences. 2018 ; Vol. 19, No. 2.
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