Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/09/04 17:31:54」(JST)

wiki en

Keratin intermediate filaments in epithelial cells (red stain).

Cytokeratins are proteins of keratin-containing intermediate filaments found in the intracytoplasmic cytoskeleton of epithelial tissue. The term "cytokeratin" began to be used in the late 1970s (for example, see "Intermediate-sized filaments of human endothelial cells" by Franke, Schmid, Osborn and Weber^[1]) when the protein subunits of keratin intermediate filaments inside cells were first being identified and characterized. In 2006 a new systematic nomenclature for keratins was created and now the proteins previously called "cytokeratins" are simply called keratins.^[2] Over 25,000 published articles exist in the biomedical research literature that used the term "cytokeratin".

Types

Micrograph showing low molecular weight cytokeratin (LMWCK) staining of intermediate trophoblast (placental tissue) and endometrial glands.

There are two types of cytokeratins: the acidic type I cytokeratins and the basic or neutral type II cytokeratins. Cytokeratins are usually found in pairs comprising a type I cytokeratin and a type II cytokeratin. Basic or neutral cytokeratins include CK1, CK2, CK3, CK4, CK5, CK6, CK7, CK8 and CK9. Acidic cytokeratins are CK10, CK12, CK 13, CK14, CK16, CK17, CK18, CK19 and CK20. The cytokeratins can be divided into low versus high molecular weight solely based on their molecular weight. Expression of these cytokeratins is frequently organ or tissue specific. As an example, CK7 is typically expressed in the ductal epithelium of the genitourinary (GU) tract and CK20 most commonly in the gastrointestinal (GI) tract.^[3] Histopathologists employ such distinctions to detect the cell of origin of various tumors.

The subsets of cytokeratins which an epithelial cell expresses depends mainly on the type of epithelium, the moment in the course of terminal differentiation and the stage of development. Thus this specific cytokeratin fingerprint allows the classification of all epithelia upon their cytokeratin expression profile. Furthermore this applies also to the malignant counterparts of the epithelia (carcinomas), as the cytokeratin profile tends to remain constant when an epithelium undergoes malignant transformation. The main clinical implication is that the study of the cytokeratin profile by immunohistochemistry techniques is a tool of immense value widely used for tumor diagnosis and characterization in surgical pathology.^[4]

Cytokeratin	Sites
Cytokeratin 4	Non-keratinized squamous epithelium, including cornea and transitional epithelium^[5]
Cytokeratin 7	A subgroup of glandular epithelia and their tumors^[5] Transitional epithelium and transitional carcinoma^[5]
Cytokeratin 8	Glandular epithelia of the digestive, respiratory and urogenital tracts, both endocrine and exocrine cells, as well as mesothelial cells Adenocarcinomas originating from those above^[5]
Cytokeratin 10	Keratinized stratified epithelium Differentiated areas of highly differentiated squamous cell carcinomas^[5]
Cytokeratin 13	Non-keratinized squamous epithelia, except cornea^[5]
Cytokeratin 14	Basal layer of stratified and combined epithelia^[5]
Cytokeratin 18	Glandular epithelia of the digestive, respiratory, and urogenital tracts, both endocrine and exocrine cells, as well as mesothelial cells Adenocarcinomas originating from those above^[5]
Cytokeratin 19	Glandular-type epithelia ^[5] Carcinomas^[5] Does not react with hepatocytes and hepatocellular carcinoma^[5]
Cytokeratin 20	Glandular-type epithelia. Signet ring/round clear cells ^[5] GI stromal tumor (Krukenberg)^[5]

Molecular biology

The cytokeratins are encoded by a family encompassing 30 genes. Among them, 20 are epithelial genes and the remaining 10 are specific for trichocytes.

All cytokeratin chains are composed of a central α-helix-rich domain (with a 50-90% sequence identity among cytokeratins of the same type and around 30% between cytokeratins of different type) with non-α-helical N- and C-terminal domains. The α-helical domain has 310-150 amino acids and comprises four segments in which a seven-residue pattern repeats. Into this repeated pattern, the first and fourth residues are hydrophobic and the charged residues show alternate positive and negative polarity, resulting in the polar residues being located on one side of the helix. This central domain of the chain provides the molecular alignment in the keratin structure and makes the chains form coiled dimers in solution.

The end-domain sequences of type I and II cytokeratin chains contain in both sides of the rod domain the subdomains V1 and V2, which have variable size and sequence. The type II also presents the conserved subdomains H1 and H2, encompassing 36 and 20 residues respectively. The subdomains V1 and V2 contain residues enriched by glycines and/or serines, the former providing the cytokeratin chain a strong insoluble character and facilitating the interaction with other molecules. These terminal domains are also important in the defining the function of the cytokeratin chain characteristic of a particular epithelial cell type.

Two dimers of cytokeratin groups into a keratin tetramer by anti-parallel binding. This cytokeratin tetramer is considered to be the main building block of the cytokeratin chain. By head-to-tail linking of the cytokeratin tetramers, the protofilaments are originated, which in turn intertwine in pairs to form protofibrils. Four protofibrils give place to one cytokeratin filament.

Cell biology

In the cytoplasm, the keratin filaments conform a complex network which extends from the surface of the nucleus to the cell membrane. Numerous accessory proteins are involved in the genesis and maintenance of such structure.

This association between the plasma membrane and the nuclear surface provides important implications for the organization of the cytoplasm and cellular communication mechanisms. Apart from the relatively static functions provided in terms of supporting the nucleus and providing tensile strength to the cell, the cytokeratin networks undergo rapid phosphate exchanges mediated depolymerization, with important implications in the more dynamic cellular processes such as mitosis and post-mitotic period, cell movement and differentiation.

Cytokeratins interact with desmosomes and hemidesmosomes, thus collaborating to cell-cell adhesion and basal cell-underlying connective tissue connection.

The intermediate filaments of the eukaryotic cytoskeleton, which the cytokeratins are one of its three components, have been probed to associate also with the ankyrin and spectrin complex protein network that underlies the cell membrane.

External links

Cytokeratin at the US National Library of Medicine Medical Subject Headings (MeSH)

References

^ Franke WW, Schmid E, Osborn M, Weber K (1979). "Intermediate-sized filaments of human endothelial cells". J Cell Biol. 81 (3): 570–580. doi:10.1083/jcb.81.3.570. PMC 2110384. PMID 379021. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2110384/.
^ Schweizer J, Bowden PE, Coulombe PA, Langbein L, Lane EB, Magin TM, Maltais L, Omary MB, Parry DA, Rogers MA, Wright MW (2006). "New consensus nomenclature for mammalian keratins". J Cell Biol. 174 (2): 169–174. doi:10.1083/jcb.200603161. PMC 2064177. PMID 16831889. http://jcb.rupress.org/cgi/content/full/174/2/169.
^ CURRENT Diagnosis & Treatment: Obstetrics & Gynecology 2011. Chapter 52. Premalignant & Malignant Disorders of the Ovaries & Oviducts. Kathleen M. Brennan, MD, Vicki V. Baker, MD, & Oliver Dorigo, MD
^ Walid MS, Osborne TJ, Robinson JS (2009). "Primary brain sarcoma or metastatic carcinoma?". Indian J Cancer 46 (2): 174–175. doi:10.4103/0019-509X.49160. PMID 19346656.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m MUbio > MONOCLONAL ANTIBODIES TO CYTOKERATINS Retrieved October 2010

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 原発不明の腺癌 adenocarcinoma of unknown primary site
2. 尿路上皮（移行上皮）膀胱癌の検出のための尿中バイオマーカー urine biomarkers for the detection of urothelial transitional cell carcinoma of the bladder
3. 胆管癌の疫学、病因、および分類 epidemiology pathogenesis and classification of cholangiocarcinoma
4. アルコール性肝炎：臨床症状および診断 alcoholic hepatitis clinical manifestations and diagnosis
5. 潜在性原発乳癌の腋窩リンパ節転移 axillary node metastases with occult primary breast cancer

English Journal

Thymoquinone Restores Radiation-Induced TGF-β Expression and Abrogates EMT in Chemoradiotherapy of Breast Cancer Cells.

Rajput S1, Kumar BN, Banik P, Parida S, Mandal M.
Journal of cellular physiology.J Cell Physiol.2015 Mar;230(3):620-9. doi: 10.1002/jcp.24780.
Radiotherapy remains a prime approach to adjuvant therapies in patients with early and advanced breast cancer. In spite of therapeutic success, metastatic progression in patients undergoing therapy, limits its application. However, effective therapeutic strategies to understand the cellular and mole
PMID 25164250

Octamer-binding protein 4 affects the cell biology and phenotypic transition of lung cancer cells involving β-catenin/E-cadherin complex degradation.

Chen ZS1, Ling DJ1, Zhang YD1, Feng JX2, Zhang XY2, Shi TS2.
Molecular medicine reports.Mol Med Rep.2015 Mar;11(3):1851-8. doi: 10.3892/mmr.2014.2992. Epub 2014 Nov 21.
Clinical studies have reported evidence for the involvement of octamer‑binding protein 4 (Oct4) in the tumorigenicity and progression of lung cancer; however, the role of Oct4 in lung cancer cell biology in vitro and its mechanism of action remain to be elucidated. Mortality among lung cancer pa
PMID 25420671

Keratins extracted from Merino wool and Brown Alpaca fibres: Thermal, mechanical and biological properties of PLLA based biocomposites.

Fortunati E1, Aluigi A2, Armentano I1, Morena F3, Emiliani C3, Martino S3, Santulli C4, Torre L1, Kenny JM1, Puglia D5.
Materials science & engineering. C, Materials for biological applications.Mater Sci Eng C Mater Biol Appl.2015 Feb;47:394-406. doi: 10.1016/j.msec.2014.11.007. Epub 2014 Nov 7.
Keratins extracted from Merino wool (KM) and Brown Alpaca fibres (KA) by sulphitolysis and commercial hydrolyzed keratins (KH) were used as fillers in poly(l-lactic) acid based biocomposites processed by solvent casting in chloroform. Different contents (1wt.% and 5wt.%) of keratins were considered
PMID 25492212

Japanese Journal

Reduced expression of cytokeratin 4 and 13 is a valuable marker for histologic grading of esophageal squamous intraepithelial neoplasia

Takashima Masaki,Kawachi Hiroshi,Yamaguchi Tsukasa,Nakajima Yutaka,Kitagaki Keisuke,Sekine Masaki,Iida Tadatsune,Takemura Kosuke,Kawano Tatsuyuki,Eishi Yoshinobu
Journal of medical and dental sciences 59(1), 17-28, 2012-03
NAID 110008904367

2)センチネルリンパ節の同定,生検による微小転移の検索 : 確実なリンパ節郭清と治療の個別化(シンポジウム2「子宮体癌治療戦略の新展開」,第63回日本産科婦人科学会・学術講演会)

新倉仁
日本産科婦人科學會雜誌 63(12), 2209-2218, 2011-12-01
… In 20 patients in whom SLNs were detected and lymph node metastases were not detected by routine histological examination, all surgically removed lymph nodes, including SLNs, were examined histopathologically by immunohistochemistry staining with an anti-cytokeratin antibody (AE1/AE3) combined with step-serial sectioning at 0.2mm intervals. …
NAID 110008799040