The Experts below are selected from a list of 30036 Experts worldwide ranked by ideXlab platform
Zhihua Liu - One of the best experts on this subject based on the ideXlab platform.
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kruppel like factor 4 promotes esophageal squamous cell carcinoma differentiation by up regulating Keratin 13 expression
Journal of Biological Chemistry, 2015Co-Authors: Yuan Hong, Haojing Zou, Hongyan Chen, Fang Ding, Yong Wan, Zhihua LiuAbstract:Abstract Squamous cell differentiation requires the coordinated activation and repression of genes specific to the differentiation process, disruption of this program accompanies malignant transformation of epithelium. The exploration of genes which control epidermal proliferation and terminal differentiation is vital to better understand esophageal carcinogenesis. KLF4 is a member of the KLF family of transcription factors and involved in both cellular proliferation and differentiation. The present study using immunohistochemistry analysis of KLF4 in clinical specimens of esophageal squamous cell carcinoma (ESCC) exhibited that decreased KLF4 was substantially associated with poor differentiation. Moreover, we determined that both KLF4 and KRT13 level were undoubtedly augmented upon sodium butyrate (SB) induced ESCC differentiation and G1-phase arrest. Conversely, silencing of KLF4 and KRT13 abrogated the inhibition of G1-S transition induced by SB. Molecular investigation demonstrated that KLF4 transcriptionally regulated KRT13 and the expression of the two molecules appreciably correlated in ESCC tissues and cell lines. Collectively, these results suggest that KLF4 transcriptionally regulates KRT13 and involves in ESCC cell differentiation.
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kruppel like factor 4 promotes esophageal squamous cell carcinoma differentiation by up regulating Keratin 13 expression
Journal of Biological Chemistry, 2015Co-Authors: Yuan Hong, Haojing Zou, Hongyan Chen, Fang Ding, Yong Wan, Zhihua LiuAbstract:Squamous cell differentiation requires the coordinated activation and repression of genes specific to the differentiation process; disruption of this program accompanies malignant transformation of epithelium. The exploration of genes that control epidermal proliferation and terminal differentiation is vital to better understand esophageal carcinogenesis. KLF4 is a member of the KLF family of transcription factors and is involved in both cellular proliferation and differentiation. This study using immunohistochemistry analysis of KLF4 in clinical specimens of esophageal squamous cell carcinoma (ESCC) demonstrated that decreased KLF4 was substantially associated with poor differentiation. Moreover, we determined that both KLF4 and KRT13 levels were undoubtedly augmented upon sodium butyrate-induced ESCC differentiation and G1 phase arrest. Conversely, silencing of KLF4 and KRT13 abrogated the inhibition of G1-S transition induced by sodium butyrate. Molecular investigation demonstrated that KLF4 transcriptionally regulated KRT13 and the expression of the two molecules appreciably correlated in ESCC tissues and cell lines. Collectively, these results suggest that KLF4 transcriptionally regulates KRT13 and is invovled in ESCC cell differentiation. Background: The transcriptional regulation of Keratin (KRT) 13 and its underlying mechanism has not been fully elucidated. Results: Up-regulation of KRT13 by Kruppel-like factor 4 (KLF4) is mediated through GKRE in the KRT13 promoter. Conclusion: KLF4 induces differentiation of ESCC by promoting KRT13 transcription. Significance: KLF4 plays a significant and previously unrecognized role in regulation of KRT13 and cell differentiation.
Yuan Hong - One of the best experts on this subject based on the ideXlab platform.
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kruppel like factor 4 promotes esophageal squamous cell carcinoma differentiation by up regulating Keratin 13 expression
Journal of Biological Chemistry, 2015Co-Authors: Yuan Hong, Haojing Zou, Hongyan Chen, Fang Ding, Yong Wan, Zhihua LiuAbstract:Abstract Squamous cell differentiation requires the coordinated activation and repression of genes specific to the differentiation process, disruption of this program accompanies malignant transformation of epithelium. The exploration of genes which control epidermal proliferation and terminal differentiation is vital to better understand esophageal carcinogenesis. KLF4 is a member of the KLF family of transcription factors and involved in both cellular proliferation and differentiation. The present study using immunohistochemistry analysis of KLF4 in clinical specimens of esophageal squamous cell carcinoma (ESCC) exhibited that decreased KLF4 was substantially associated with poor differentiation. Moreover, we determined that both KLF4 and KRT13 level were undoubtedly augmented upon sodium butyrate (SB) induced ESCC differentiation and G1-phase arrest. Conversely, silencing of KLF4 and KRT13 abrogated the inhibition of G1-S transition induced by SB. Molecular investigation demonstrated that KLF4 transcriptionally regulated KRT13 and the expression of the two molecules appreciably correlated in ESCC tissues and cell lines. Collectively, these results suggest that KLF4 transcriptionally regulates KRT13 and involves in ESCC cell differentiation.
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kruppel like factor 4 promotes esophageal squamous cell carcinoma differentiation by up regulating Keratin 13 expression
Journal of Biological Chemistry, 2015Co-Authors: Yuan Hong, Haojing Zou, Hongyan Chen, Fang Ding, Yong Wan, Zhihua LiuAbstract:Squamous cell differentiation requires the coordinated activation and repression of genes specific to the differentiation process; disruption of this program accompanies malignant transformation of epithelium. The exploration of genes that control epidermal proliferation and terminal differentiation is vital to better understand esophageal carcinogenesis. KLF4 is a member of the KLF family of transcription factors and is involved in both cellular proliferation and differentiation. This study using immunohistochemistry analysis of KLF4 in clinical specimens of esophageal squamous cell carcinoma (ESCC) demonstrated that decreased KLF4 was substantially associated with poor differentiation. Moreover, we determined that both KLF4 and KRT13 levels were undoubtedly augmented upon sodium butyrate-induced ESCC differentiation and G1 phase arrest. Conversely, silencing of KLF4 and KRT13 abrogated the inhibition of G1-S transition induced by sodium butyrate. Molecular investigation demonstrated that KLF4 transcriptionally regulated KRT13 and the expression of the two molecules appreciably correlated in ESCC tissues and cell lines. Collectively, these results suggest that KLF4 transcriptionally regulates KRT13 and is invovled in ESCC cell differentiation. Background: The transcriptional regulation of Keratin (KRT) 13 and its underlying mechanism has not been fully elucidated. Results: Up-regulation of KRT13 by Kruppel-like factor 4 (KLF4) is mediated through GKRE in the KRT13 promoter. Conclusion: KLF4 induces differentiation of ESCC by promoting KRT13 transcription. Significance: KLF4 plays a significant and previously unrecognized role in regulation of KRT13 and cell differentiation.
Gail S Prins - One of the best experts on this subject based on the ideXlab platform.
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Keratin profiling by single cell rna sequencing identifies human prostate stem cell lineage hierarchy and cancer stem like cells
International Journal of Molecular Sciences, 2021Co-Authors: Lishi Xie, Larisa Nonn, Michael R Abern, Toshihiro Shioda, Gail S PrinsAbstract:Single prostate stem cells can generate stem and progenitor cells to form prostaspheres in 3D culture. Using a prostasphere-based label retention assay, we recently identified Keratin 13 (KRT13)-enriched prostate stem cells at single-cell resolution, distinguishing them from daughter progenitors. Herein, we characterized the epithelial cell lineage hierarchy in prostaspheres using single-cell RNA-seq analysis. Keratin profiling revealed three clusters of label-retaining prostate stem cells; cluster I represents quiescent stem cells (PSCA, CD36, SPINK1, and KRT13/23/80/78/4 enriched), while clusters II and III represent active stem and bipotent progenitor cells (KRT16/17/6 enriched). Gene set enrichment analysis revealed enrichment of stem and cancer-related pathways in cluster I. In non-label-retaining daughter progenitor cells, three clusters were identified; cluster IV represents basal progenitors (KRT5/14/6/16 enriched), while clusters V and VI represent early and late-stage luminal progenitors, respectively (KRT8/18/10 enriched). Furthermore, MetaCore analysis showed enrichment of the "cytoskeleton remodeling-Keratin filaments" pathway in cancer stem-like cells from human prostate cancer specimens. Along with common Keratins (KRT13/23/80/78/4) in normal stem cells, unique Keratins (KRT10/19/6C/16) were enriched in cancer stem-like cells. Clarification of these Keratin profiles in human prostate stem cell lineage hierarchy and cancer stem-like cells can facilitate the identification and therapeutic targeting of prostate cancer stem-like cells.
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abstract 3063 stem cell lineage hierarchy by Keratin profiling in normal human prostate epithelial cells and prostate cancer
Cancer Research, 2018Co-Authors: Lishi Xie, Larisa Nonn, Toshi Shioda, Gail S PrinsAbstract:Background: Both mechanical and nonmechanical functions of Keratins have been implicated in stem cells and cancers. Using a sphere-based label retention assay, we recently isolated and characterized prostate stem cells and cancer stem-like cells from mixed progenitor populations (PMID 28651114), identifying Keratin 13 (KRT13) as a specific prostate stem cell marker regulating self-renewal. Herein we utilize detailed Keratin profiles to further clarify the human prostate epithelial lineage hierarchy and identify prostate cancer stem-like cells. Methods and Results: Primary prostate epithelial cells were 3D cultured (5 days) to form prostaspheres (PS), followed by PS-based long-term label retention and FACS to separate stem cells from progenitors. In normal prostate tissues from three healthy donors, RNA-seq revealed enrichment of KRT13, 23, 80, 78, 86 and 4 in label-retaining prostate stem cells while KRT6, 17, 14, 5, 8, 18 and P63 were enriched in nonretaining progenitors. We next used Fluidigm C1 captured single-cell RNA-seq and identified three major clusters in the label-retaining stem cell population; Cluster I represents quiescent stem cells (KRT13, 23, 80, 78, 4 enriched) and Clusters II and III contain active stem cells and bipotent progenitors, respectively (KRT16, 17, 6 enriched). GSEA analysis found stem cell and cancer-related pathways enrichment in Cluster I. Three additional clusters were identified in nonretaining progenitor cells, with Cluster IV representing unipotent basal progenitor cells (KRT5, 14, 6, 16 enriched) and Clusters V and VI early- and late-stage unipotent luminal progenitors (KRT8, 18, 10 enriched). Cancer stem-like cells were similarly isolated from three prostate cancer specimens and RNA-seq with MetaCore pathway analysis found enrichment of cytoskeleton remodeling Keratin filaments. Interestingly, in addition to normal stem cell Keratins (KRT13, 23, 80, 78, 4), other Keratins (KRT10, 19, 6, 75, 16, 79, 3, 82) were enriched in cancer stem-like cells. Surprisingly, stem-like cells from patient-matched benign regions revealed a similar Keratin profile, suggesting a cancer field effect for stem-like cell populations. Conclusion: Taken together, using gene profiling with an emphasis on Keratin patterns, we have delineated the lineage hierarchy of human prostate stem cells originating from the activation of quiescent stem cells to bipotent progenitors that give rise to unipotent basal and luminal progenitor cells. We have identified common Keratins enriched in stem cells from normal prostate and cancer/benign tissues as well as Keratins unique in stem-like cells from prostate cancer. This clarification of the stem cell lineage hierarchy and Keratin profiling of human prostate stem cells and cancer stem-like cells may provide enhanced opportunities for translational studies that target therapeutic-resistant cancer stem-like cells. (CA-172220) Citation Format: Wenyang Hu, Danping Hu, Lishi Xie, Hong Hu, Ye Li, Larisa Nonn, Toshi Shioda, Gail S. Prins. Stem cell lineage hierarchy by Keratin profiling in normal human prostate epithelial cells and prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3063.
Traian V. Chirila - One of the best experts on this subject based on the ideXlab platform.
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Evaluation of the AlgerBrush II rotating burr as a tool for inducing ocular surface failure in the New Zealand White rabbit
2016Co-Authors: Elham Nili, Jennifer Walshe, Neil A. Richardson, Ivan R. Schwab, Cora Lau, Brendan G. Cronin, Lawrence W. Hirst, Barnett Nigel, Traian V. ChirilaAbstract:The New Zealand White rabbit has been widely used as a model of limbal stem cell deficiency (LSCD). Current techniques for experimental induction of LSCD utilize caustic chemicals, or organic solvents applied in conjunction with a surgical limbectomy. While generally successful in depleting epithelial progenitors, the depth and severity of injury is difficult to control using chemical-based methods. Moreover, the anterior chamber can be easily perforated while surgically excising the corneal limbus. In the interest of creating a safer and more defined LSCD model, we have therefore evaluated a mechanical debridement technique based upon use of the AlgerBrush II rotating burr. An initial comparison of debridement techniques was conducted in situ using 24 eyes in freshly acquired New Zealand White rabbit cadavers. Techniques for comparison (4 eyes each) included: (1) non-wounded control, (2) surgical limbectomy followed by treatment with 100% (v/v) n-heptanol to remove the corneal epithelium (1-2 minutes), (3) treatment of both limbus and cornea with n-heptanol alone, (4) treatment of both limbus and cornea with 20% (v/v) ethanol (2-3 minutes), (5) a 2.5-mm rounded burr applied to both the limbus and cornea, and (6) a 1-mm pointed burr applied to the limbus, followed by the 2.5-mm rounded burr applied to the cornea. All corneas were excised and processed for histology immediately following debridement. A panel of four assessors subsequently scored the degree of epithelial debridement within the cornea and limbus using masked slides. The 2.5-mm burr most consistently removed the corneal and limbal epithelia. Islands of limbal epithelial cells were occasionally retained following surgical limbectomy/heptanol treatment, or use of the 1-mm burr. Limbal epithelial cells were consistently retained following treatment with either ethanol or n-heptanol alone, with ethanol being the least effective treatment overall. The 2.5-mm burr method was subsequently evaluated in the right eye of 3 live rabbits by weekly clinical assessments (photography and slit lamp examination) for up to 5 weeks, followed by histological analyses (hematoxylin & eosin stain, periodic acid-Schiff stain and immunohistochemistry for Keratin 3 and 13). All 3 eyes that had been completely debrided using the 2.5-mm burr displayed symptoms of ocular surface failure as defined by retention of a prominent epithelial defect (~40% of corneal surface at 5 weeks), corneal neovascularization (2 to 3 quadrants), reduced corneal transparency and conjunctivalization of the corneal surface (demonstrated by the presence of goblet cells and/or staining for Keratin 13). In conclusion, our findings indicate that the AlgerBrush II rotating burr is an effective method for the establishment of ocular surface failure in New Zealand White rabbits. In particular, we recommend use of the 2.5-mm rotating burr for improved efficiency of epithelial debridement and safety compared to surgical limbectomy.
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Evaluation of the AlgerBrush II rotating burr as a tool for inducing ocular surface failure in the New Zealand White rabbit
Experimental eye research, 2016Co-Authors: Elham Nili, Jennifer Walshe, Neil A. Richardson, Ivan R. Schwab, Cora Lau, Nigel L. Barnett, Brendan G. Cronin, Lawrence W. Hirst, Traian V. ChirilaAbstract:The New Zealand White rabbit has been widely used as a model of limbal stem cell deficiency (LSCD). Current techniques for experimental induction of LSCD utilize caustic chemicals, or organic solvents applied in conjunction with a surgical limbectomy. While generally successful in depleting epithelial progenitors, the depth and severity of injury is difficult to control using chemical-based methods. Moreover, the anterior chamber can be easily perforated while surgically excising the corneal limbus. In the interest of creating a safer and more defined LSCD model, we have therefore evaluated a mechanical debridement technique based upon use of the AlgerBrush II rotating burr. An initial comparison of debridement techniques was conducted in situ using 24 eyes in freshly acquired New Zealand White rabbit cadavers. Techniques for comparison (4 eyes each) included: (1) non-wounded control, (2) surgical limbectomy followed by treatment with 100% (v/v) n-heptanol to remove the corneal epithelium (1-2 min), (3) treatment of both limbus and cornea with n-heptanol alone, (4) treatment of both limbus and cornea with 20% (v/v) ethanol (2-3 min), (5) a 2.5-mm rounded burr applied to both the limbus and cornea, and (6) a 1-mm pointed burr applied to the limbus, followed by the 2.5-mm rounded burr applied to the cornea. All corneas were excised and processed for histology immediately following debridement. A panel of four assessors subsequently scored the degree of epithelial debridement within the cornea and limbus using masked slides. The 2.5-mm burr most consistently removed the corneal and limbal epithelia. Islands of limbal epithelial cells were occasionally retained following surgical limbectomy/heptanol treatment, or use of the 1-mm burr. Limbal epithelial cells were consistently retained following treatment with either ethanol or n-heptanol alone, with ethanol being the least effective treatment overall. The 2.5-mm burr method was subsequently evaluated in the right eye of 3 live rabbits by weekly clinical assessments (photography and slit lamp examination) for up to 5 weeks, followed by histological analyses (hematoxylin & eosin stain, periodic acid-Schiff stain and immunohistochemistry for Keratin 3 and 13). All 3 eyes that had been completely debrided using the 2.5-mm burr displayed symptoms of ocular surface failure as defined by retention of a prominent epithelial defect (∼40% of corneal surface at 5 weeks), corneal neovascularization (2-3 quadrants), reduced corneal transparency and conjunctivalization of the corneal surface (demonstrated by the presence of goblet cells and/or staining for Keratin 13). In conclusion, our findings indicate that the AlgerBrush II rotating burr is an effective method for the establishment of ocular surface failure in New Zealand White rabbits. In particular, we recommend use of the 2.5-mm rotating burr for improved efficiency of epithelial debridement and safety compared to surgical limbectomy.
Yong Wan - One of the best experts on this subject based on the ideXlab platform.
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kruppel like factor 4 promotes esophageal squamous cell carcinoma differentiation by up regulating Keratin 13 expression
Journal of Biological Chemistry, 2015Co-Authors: Yuan Hong, Haojing Zou, Hongyan Chen, Fang Ding, Yong Wan, Zhihua LiuAbstract:Abstract Squamous cell differentiation requires the coordinated activation and repression of genes specific to the differentiation process, disruption of this program accompanies malignant transformation of epithelium. The exploration of genes which control epidermal proliferation and terminal differentiation is vital to better understand esophageal carcinogenesis. KLF4 is a member of the KLF family of transcription factors and involved in both cellular proliferation and differentiation. The present study using immunohistochemistry analysis of KLF4 in clinical specimens of esophageal squamous cell carcinoma (ESCC) exhibited that decreased KLF4 was substantially associated with poor differentiation. Moreover, we determined that both KLF4 and KRT13 level were undoubtedly augmented upon sodium butyrate (SB) induced ESCC differentiation and G1-phase arrest. Conversely, silencing of KLF4 and KRT13 abrogated the inhibition of G1-S transition induced by SB. Molecular investigation demonstrated that KLF4 transcriptionally regulated KRT13 and the expression of the two molecules appreciably correlated in ESCC tissues and cell lines. Collectively, these results suggest that KLF4 transcriptionally regulates KRT13 and involves in ESCC cell differentiation.
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kruppel like factor 4 promotes esophageal squamous cell carcinoma differentiation by up regulating Keratin 13 expression
Journal of Biological Chemistry, 2015Co-Authors: Yuan Hong, Haojing Zou, Hongyan Chen, Fang Ding, Yong Wan, Zhihua LiuAbstract:Squamous cell differentiation requires the coordinated activation and repression of genes specific to the differentiation process; disruption of this program accompanies malignant transformation of epithelium. The exploration of genes that control epidermal proliferation and terminal differentiation is vital to better understand esophageal carcinogenesis. KLF4 is a member of the KLF family of transcription factors and is involved in both cellular proliferation and differentiation. This study using immunohistochemistry analysis of KLF4 in clinical specimens of esophageal squamous cell carcinoma (ESCC) demonstrated that decreased KLF4 was substantially associated with poor differentiation. Moreover, we determined that both KLF4 and KRT13 levels were undoubtedly augmented upon sodium butyrate-induced ESCC differentiation and G1 phase arrest. Conversely, silencing of KLF4 and KRT13 abrogated the inhibition of G1-S transition induced by sodium butyrate. Molecular investigation demonstrated that KLF4 transcriptionally regulated KRT13 and the expression of the two molecules appreciably correlated in ESCC tissues and cell lines. Collectively, these results suggest that KLF4 transcriptionally regulates KRT13 and is invovled in ESCC cell differentiation. Background: The transcriptional regulation of Keratin (KRT) 13 and its underlying mechanism has not been fully elucidated. Results: Up-regulation of KRT13 by Kruppel-like factor 4 (KLF4) is mediated through GKRE in the KRT13 promoter. Conclusion: KLF4 induces differentiation of ESCC by promoting KRT13 transcription. Significance: KLF4 plays a significant and previously unrecognized role in regulation of KRT13 and cell differentiation.
