Keratin 17 identified by proteomic analysis may be involved in tumor angiogenesis

Xu, Yong; Zhang, Suzhen; Huang, Canhua; Liu, Xinyu; Zhong, Zhenhua; Hou, Wen-Li; Su, Zi-Fen; Wei, Yuquan

doi:10.5483/bmbrep.2009.42.6.344

Cited by 10 publications

(11 citation statements)

References 22 publications

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“…Keratin filaments are essential intracellular components that modulate intracellular signaling involved in cell growth and angiogenesis (Xu et al, 2009;Chung et al, 2012). Fibroblast and endothelial cell culture show that some keratins also have non-structural roles in intracellular signaling and vascular growth through angiogenesis (Katagata et al, 2002;Xu et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Fibroblast and endothelial cell culture show that some keratins also have non-structural roles in intracellular signaling and vascular growth through angiogenesis (Katagata et al, 2002;Xu et al, 2009). Therefore, it may be possible that a worse radiotherapy response in patients with low K17 expression is due to less oxygen permeating tumor cells and consequently a lower production of oxygen reactive species (ROS), which are necessary for lethal damage after radiotherapy (Karar and Maity, 2009).…”

Section: Discussionmentioning

confidence: 99%

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Keratins 17 and 19 expression as prognostic markers in oral squamous cell carcinoma

Coelho¹,

Peterle²,

Santos³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Five-year survival rates for oral squamous cell carcinoma (OSCC) are 30% and the mortality rate is 50%. Immunohistochemistry panels are used to evaluate proliferation, vascularization, apoptosis, HPV infection, and keratin expression, which are important markers of malignant progression. Keratins are a family of intermediate filaments predominantly expressed in epithelial cells and have an essential role in mechanical support and cytoskeleton formation, which is essential for the structural integrity and stability of the cell. In this study, we analyzed the expressions of keratins 17 and 19 (K17 and K19) by immunohistochemistry in tumoral and non-tumoral tissues from patients with OSCC. The results show that expression of these keratins is higher in tumor tissues compared to non-tumor tissues. Positive K17 expression correlates with lymph node metastasis and multivariate analysis confirmed this relationship, revealing a 6-fold increase in lymph node metastasis when K17 is expressed. We observed a correlation between K17 expression with disease-free survival and disease-specific death in patients who received surgery and radiotherapy. Multivariate analysis revealed that low expression of K17 was an independent marker for early disease relapse and disease-specific death in patients treated with surgery and radiotherapy, with an approximately 4-fold increased risk when compared to high K17 expression. Our results suggest a potential role for K17 and K19 expression profiles as tumor prognostic markers in OSCC patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Keratins 17 and 19 expression as prognostic markers in oral squamous cell carcinoma

Coelho¹,

Peterle²,

Santos³

et al. 2015

Genet. Mol. Res.

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“…It has been shown that the treatment of cultured blastemal cells with K8 and K18 antisense oligonucleotides significantly decreases DNA synthesis and induces differences in cell morphology (18). The inverse association of keratin 17 imparts a decisive role in regeneration because it is shown that the intermediate filament protein, keratin 17, has been involved in inducing the wounded stratified epithelia for regulation of cell growth (19), promoting epithelial proliferation and tumor growth by polarizing the immune response (20), and inducing tumor angiogenesis (21).…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Zebrafish Caudal Fin Regeneration

Saxena

Singh

Lakshmi

et al. 2012

Molecular & Cellular Proteomics

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The epimorphic regeneration of zebrafish caudal fin is rapid and complete. We have analyzed the biomechanism of zebrafish caudal fin regeneration at various time points based on differential proteomics approaches. The spectrum of proteome changes caused by regeneration were analyzed among controls (0 h) and 1, 12, 24, 48, and 72 h postamputation involving quantitative differential proteomics analysis based on two-dimensional gel electrophoresis matrix-assisted laser desorption/ionization and differential in-gel electrophoresis Orbitrap analysis. A total of 96 proteins were found differentially regulated between the control nonregenerating and regenerating tissues of different time points for having at least 1.5-fold changes. 90 proteins were identified as differentially regulated for regeneration based on differential in-gel electrophoresis analysis between the control and regenerating tissues. 35 proteins were characterized for its expression in all of the five regenerating time points against the control samples. The proteins identified and associated with regeneration were found to be directly allied with various molecular, biological, and cellular functions. Based on network pathway analysis, the identified proteome data set for regeneration was majorly associated in maintaining cellular structure and architecture. Also the proteins were found associated for the cytoskeleton remodeling pathway and cellular immune defense mechanism. The major proteins that were found differentially regulated during zebrafish caudal fin regeneration includes keratin and its 10 isoforms, cofilin 2, annexin a1, skeletal ␣1 actin, and structural proteins. Annexin A1 was found to be exclusively undergoing phosphorylation during regeneration. The obtained differential proteome and the direct association of the various proteins might lead to a new understanding of the regeneration mechanism. Molecular & Cellular Proteomics 11: 10.1074/mcp.M111.014118, 1-19, 2012.Regeneration is an important mechanism found among most of the animals including humans in various tissues and organs towards growth, regrowth, repair, reproduction, and survival. The biomechanism of regeneration has been widely studied but poorly understood because of its different extents in various animals. Understanding the basic molecular mechanism of regeneration in the wound environment is of high significance, because it can lead to an applied possibility of making nonregenerating to a regenerating system.Tissue regeneration in vertebrates is found with extensive capabilities. Regeneration of limbs in urodele and caudal fin in zebrafish are the most projected regeneration studies among vertebrates. Zebrafish regenerates a wide variety of tissue structures including heart, fin, spinal cord, and optic nerve (1-3) based on the characteristic regeneration mechanism involving epithelialization, mesenchymal disorganization, blastema formation, regenerative outgrowth, and termination.A great number of gene families, counting wnt, hox, fgf, fgfr, and msx genes, were shown to...

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“…The expression of KRT17 has been found to be up-regulated in cancerous tissues in cervical [56], tongue [57], oral [58], and esophageal squamous cell carcinomas [59]. Increased expression of keratin 17 in endothelial cells may contribute to angiogenesis [60] and may promote epithelial proliferation and tumor growth [31]. Keratin 17 has also been reported as a potential diagnostic marker for oral squamous cell carcinoma [58], and it might be linked to the clinical progression and differentiation of cervical carcinoma [61], [62].…”

Section: Discussionmentioning

confidence: 99%

A Systematic Analysis on DNA Methylation and the Expression of Both mRNA and microRNA in Bladder Cancer

et al. 2011

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BackgroundDNA methylation aberration and microRNA (miRNA) deregulation have been observed in many types of cancers. A systematic study of methylome and transcriptome in bladder urothelial carcinoma has never been reported.Methodology/Principal FindingsThe DNA methylation was profiled by modified methylation-specific digital karyotyping (MMSDK) and the expression of mRNAs and miRNAs was analyzed by digital gene expression (DGE) sequencing in tumors and matched normal adjacent tissues obtained from 9 bladder urothelial carcinoma patients. We found that a set of significantly enriched pathways disrupted in bladder urothelial carcinoma primarily related to “neurogenesis” and “cell differentiation” by integrated analysis of -omics data. Furthermore, we identified an intriguing collection of cancer-related genes that were deregulated at the levels of DNA methylation and mRNA expression, and we validated several of these genes (HIC1, SLIT2, RASAL1, and KRT17) by Bisulfite Sequencing PCR and Reverse Transcription qPCR in a panel of 33 bladder cancer samples.Conclusions/SignificanceWe characterized the profiles between methylome and transcriptome in bladder urothelial carcinoma, identified a set of significantly enriched key pathways, and screened four aberrantly methylated and expressed genes. Conclusively, our findings shed light on a new avenue for basic bladder cancer research.

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Keratin 17 identified by proteomic analysis may be involved in tumor angiogenesis

Cited by 10 publications

References 22 publications

Keratins 17 and 19 expression as prognostic markers in oral squamous cell carcinoma

Keratins 17 and 19 expression as prognostic markers in oral squamous cell carcinoma

Proteomic Analysis of Zebrafish Caudal Fin Regeneration

A Systematic Analysis on DNA Methylation and the Expression of Both mRNA and microRNA in Bladder Cancer

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