Cytokeratin 

Introduction

Keratins (cytokeratins) are intermediate filament proteins that are mainly expressed in epithelial cells. Keratin heterodimers composed of an acidic keratin (or type I keratin, keratins K9-K28) and a basic keratin (or type II keratin, keratins K1-K8 and K71-K80) assemble to form filaments. Keratin isoforms demonstrate tissue- and differentiation-specific profiles that make them useful as research and clinical biomarkers.

Dysregulation/mutations in keratin genes can lead to a variety of disorders affecting the skin, hair, nails, and other epithelial tissues. While expression of keratins can be variable, immunohistochemical staining of keratins is widely used to help in the identification and classification of epithelial tumors, and may also provide prognostic information.

Keratin Expression Profiles

Keratins 8 and 18 (K8/K18) are expressed in simple epithelia of normal tissue, as well as in adenocarcinomas of the breast, lung, ovary, and gastrointestinal tract. Keratin 17 is expressed in basal keratinocytes of stratified epithelia, hair follicles, and sebaceous glands. Onset of keratin 17 expression coincides with the definition of major epithelial lineages during skin development. Keratin 14 (K14) is expressed in basal cells of stratified epithelia, and in basal-like subtypes of breast cancer and squamous cell carcinomas. Keratin 19 (K19) is expressed in glandular epithelia, including the liver, gallbladder, and pancreas, as well as in adenocarcinomas of the breast, thyroid, and bile duct. Keratin 20 (K20) is expressed in gastrointestinal epithelium, urothelium, and Merkel cells in the skin, as well as in colorectal carcinomas and some urothelial carcinomas. Keratin 5/6 (K5/6) is expressed in basal cells of stratified epithelia, including the skin, prostate, and breast, as well as in basal-like breast cancers, squamous cell carcinomas, and some lung carcinomas. Keratin 7 (K7) is expressed in glandular epithelia, such as those in the lung, breast, and female reproductive tract, as well as in adenocarcinomas of the lung, breast, and ovary.

Keratins, particularly K8, K18, and K19, serve as biomarkers for identification of circulating tumor cells (CTCs).

Post-translational modifications, including phosphorylation, acetylation, ubiquitylation, sumoylation, glycosylation, and transamidation, have been shown to affect the functions of keratins in normal and disease states. Understanding the molecular mechanisms underlying these PTMs may provide insights into cancer pathogenesis.

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References

• Chang L, Goldman RD. Intermediate filaments mediate cytoskeletal crosstalk. Nat Rev Mol Cell Biol. 2004 Aug;5(8):601-13. [PMID: 15366704].

• Schweizer J, Bowden PE, Coulombe PA,et,al. New consensus nomenclature for mammalian keratins. J Cell Biol. 2006 Jul 17;174(2):169-74. Epub 2006 Jul 10. [PMID: 16831889].

• Sarma A. Biological importance and pharmaceutical significance of keratin: A review. Int J Biol Macromol. 2022 Oct 31;219:395-413.2022.08.002. Epub 2022 Aug 5. [PMID: 35934081].

• McGowan KM, Coulombe PA. Onset of keratin 17 expression coincides with the definition of major epithelial lineages during skin development. J Cell Biol. 1998 Oct 19;143(2):469-86. [PMID: 9786956].

• Werner S, Keller L, Pantel K. Epithelial keratins: Biology and implications as diagnostic markers for liquid biopsies. Mol Aspects Med. 2020 Apr;72:100817. 2019.09.001. Epub 2019 Sep 25. [PMID: 31563278].

• Dmello C, Srivastava SS, Tiwari R, et,al. Multifaceted role of keratins in epithelial cell differentiation and transformation. J Biosci. 2019 Jun;44(2):33.[PMID: 31180046].

Flora Flora is a technical support expert at EnkiLife, familiar with immunology and neuroscience, dedicated to providing customers with high-quality product combinations and technical support to help achieve research in neurodegenerative diseases and other neuroscience areas.