Cytokeratin-8 in Anaplastic Thyroid Carcinoma: More Than a Simple Structural Cytoskeletal Protein
AbstractAnaplastic 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
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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.
Guo D, Xu Q, Pabla S, Koomen J, Biddinger P, Sharma A, Pabla S, Pacholczyk R, Chang C-C, Friedrich K, Mohammed K, Smallridge RC, Copland JA, She J-X, Weinberger PM. Cytokeratin-8 in Anaplastic Thyroid Carcinoma: More Than a Simple Structural Cytoskeletal Protein. International Journal of Molecular Sciences. 2018; 19(2):577.Chicago/Turabian Style
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. 2018. "Cytokeratin-8 in Anaplastic Thyroid Carcinoma: More Than a Simple Structural Cytoskeletal Protein." Int. J. Mol. Sci. 19, no. 2: 577.
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