Biological Functions of Cytokeratin 18 in Cancer

Weng, Yiwu; Cui, Yun; Fang, Jing‐Yuan

doi:10.1158/1541-7786.mcr-11-0222

Cited by 90 publications

(75 citation statements)

References 71 publications

(140 reference statements)

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“…There are twenty diferent keratin polypeptides (K1-K20) identiied and classiied into type I (K9-K20) and type II (K1-K8) intermediate ilaments [73]. Keratins of importance to cancer therapy are keratin 8 (K8) and keratin 18 (K18), the most common and characteristic members of intermediate ilaments expressed in single-layer epithelial tissues [74,75]. Oncogenes, which activate Ras signaling, stimulate expression of K18 through transcription factors [76].…”

Section: Anti-keratin Agentsmentioning

confidence: 99%

Targeting the Cytoskeleton with Plant-Bioactive Compounds in Cancer Therapy

Ardelean¹

2017

Cytoskeleton - Structure, Dynamics, Function and Disease

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In this overview we describe the main plant-derived bioactive compounds used in cancer therapy which has the cell cytoskeleton as therapeutic target. Three major classes of these compounds are described: antimitotics with microtubule-destabilizing and-stabilizing efects, plant-bioactive compounds that interact with intermediate ilaments/actin, and plant-bioactive compounds that interact with intermediate ilaments like keratins and vimentin. We also focus on the molecular aspects of interactions with their cellular targets: microtubules, intermediate ilaments, and microilaments. Some critical aspects of cardiac side efects of cancer chemotherapy are also discussed, focusing on cardiac cytoskeleton and protective efect of plant-derived compounds. The application of plant bioactives in the treatment of cancer has resulted in increased therapeutic eicacy through targeting the cytoskeleton, respectively, prevention of the injury of cytoskeletal components elicited by chemotherapeutics.

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Section: Anti-keratin Agentsmentioning

confidence: 99%

Targeting the Cytoskeleton with Plant-Bioactive Compounds in Cancer Therapy

Ardelean¹

2017

Cytoskeleton - Structure, Dynamics, Function and Disease

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“…KRT18 (cytokeratin 18) is involved in multiple cellular processes including apoptosis, mitosis, cell cycle progression, and cell signaling and is hypothesized to be involved in carcinogenesis through multiple signaling pathways. 27 Therefore, the pseudogene mediated upregulation of KRT18 may lead to the aberrant regulation of signaling pathways in ALL.…”

Section: Differential Expression Of Transcripts With Epigenetic Regulmentioning

confidence: 99%

Integrated methylome and transcriptome analysis reveals novel regulatory elements in pediatric acute lymphoblastic leukemia

et al. 2015

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Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children under the age of 15. In addition to genetic aberrations, epigenetic modifications such as DNA methylation are altered in cancer and impact gene expression. To identify epigenetic alterations in ALL, genome-wide methylation profiles were generated using the methylated CpG island recovery assay followed by next-generation sequencing. More than 25,000 differentially methylated regions (DMR) were observed in ALL patients with »90% present within intronic or intergenic regions. To determine the regulatory potential of the DMR, whole-transcriptome analysis was performed and integrated with methylation data. Aberrant promoter methylation was associated with the altered expression of genes involved in transcriptional regulation, apoptosis, and proliferation. Novel enhancer-like sequences were identified within intronic and intergenic DMR. Aberrant methylation in these regions was associated with the altered expression of neighboring genes involved in cell cycle processes, lymphocyte activation and apoptosis. These genes include potential epi-driver genes, such as SYNE1, PTPRS, PAWR, HDAC9, RGCC, MCOLN2, LYN, TRAF3, FLT1, and MELK, which may provide a selective advantage to leukemic cells. In addition, the differential expression of epigenetic modifier genes, pseudogenes, and non-coding RNAs was also observed accentuating the role of erroneous epigenetic gene regulation in ALL.

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“…CK18 is involved in important cellular processes including apoptosis, mitosis, cell cycle progression, and cell signaling under normal physiological conditions. Circulating CK18 fragments have been accepted as an epithelial marker for diagnostic histopathological examinations, and has been suggested to affect tumor cell behaviors (Weng et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of serum HGF and CK18 levels in patients with esophageal cancer

Kilic-Baygutalp¹,

Öztürk²,

Orsal-Ibisoglu³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Cytokeratins are thought to play a role in apoptosis. Cytokeratin 18 (CK18) is involved in the formation of intracellular cytoskeleton, and has been considered a promising apoptosis marker in gastrointestinal carcinomas. Growth factors, including hepatocyte growth factor (HGF), may provide a microenvironment for malignant cells. In this study, we aimed to compare serum HGF and CK18 levels between esophageal squamous cell carcinoma patients and healthy controls. The study included 41 adult patients (20 male, 21 female) diagnosed with esophageal squamous cell carcinoma, with a mean age of 63.54 ± 10.88 years (range, 41-82 years). We also recruited 39 age and gender-matched healthy control subjects. Venous blood samples were taken; serum HGF and CK18 concentrations were determined via ELISA. Results indicated that serum HGF levels were higher in patients (1.37 ± 0.63 ng/mL) as compared to the healthy subjects (0.41 ± 0.29 ng/mL). Similarly, serum CK18 levels were higher in the patient group (2.53 ± 1.33 ng/mL) than in the control group (0.34 ± 0.23 ng/mL) (P < 0.001). In addition, serum HGF and CK18 levels were positively correlated with metastasis stage, tumor stage, and disease stage of esophageal squamous cell carcinoma. To our knowledge, this is the first study to evaluate serum HGF and CK18 levels in patients with esophageal squamous cell carcinoma. The results suggest that serum CK18 and HGF levels may be used as prognostic and disease monitoring biomarkers of esophageal squamous cell carcinoma.

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Biological Functions of Cytokeratin 18 in Cancer

Cited by 90 publications

References 71 publications

Targeting the Cytoskeleton with Plant-Bioactive Compounds in Cancer Therapy

Targeting the Cytoskeleton with Plant-Bioactive Compounds in Cancer Therapy

Integrated methylome and transcriptome analysis reveals novel regulatory elements in pediatric acute lymphoblastic leukemia

Evaluation of serum HGF and CK18 levels in patients with esophageal cancer

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