@article{5a4ef59ca921499d8ed59cfa0618bae0,
title = "Cytokeratin-8 in anaplastic thyroid carcinoma: More than a simple structural cytoskeletal protein",
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.",
keywords = "Anaplastic thyroid carcinoma, Apoptosis, Cytokeratin-8",
author = "Dehuang Guo and Qinqin Xu and Sarabjot Pabla and John Koomen and Biddinger, {Paul Williams} and Sharma, {Ashok Kumar} and Simarjot Pabla and Pacholczyk, {Rafal W} and Chang, {Chien Chung} and Kevin Friedrich and Kamran Mohammed and Smallridge, {Robert C.} and Copland, {John A.} and Jin-Xiong She and Weinberger, {Paul M.}",
note = "Funding Information: The authors would like to thank Nita Maihle and William David Hill for review of this manuscript, the Augusta University Electron Microscopy and Histology Core for assistance with tissue microarray (TMA) slide sectioning, the National Cancer Institute, American Academy of Otolaryngology/Head and Neck Surgery and American Head and Neck Society who provided funding (PMW) that enabled early progress leading to this study. This study was internally funded by the corresponding author{\textquoteright}s institutional startup funds (PMW) and by the Ministry of Science and Technology grants MOST-103-2320-B-007-005 and MOST-104-2320-B-007-002 (CCC). Funding Information: Acknowledgments: The authors would like to thank Nita Maihle and William David Hill for review of this manuscript, the Augusta University Electron Microscopy and Histology Core for assistance with tissue microarray (TMA) slide sectioning, the National Cancer Institute, American Academy of Otolaryngology/Head and Neck Surgery and American Head and Neck Society who provided funding (PMW) that enabled early progress leading to this study. This study was internally funded by the corresponding author{\textquoteright}s institutional startup funds (PMW) and by the Ministry of Science and Technology grants MOST-103-2320-B-007-005 and MOST-104-2320-B-007-002 (CCC). Publisher Copyright: {\textcopyright} 2018 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2018",
month = feb,
day = "14",
doi = "10.3390/ijms19020577",
language = "English (US)",
volume = "19",
journal = "International journal of molecular sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "2",
}
