LIVIVO - Search results -

Search results

Result 1 - 10 of total 35

Search options

Article ; Online: Inactivation of the Tumor Suppressor CYLD Sensitizes Mice to Breast Cancer Development.

Pseftogas, Athanasios / Xanthopoulos, Konstantinos / Siasiaridis, Athanasios / Poutahidis, Theofilos / Gonidas, Christos / Tsingotjidou, Anastasia / Hatzivassiliou, Eudoxia / Mosialos, George

Anticancer research

2024 Volume 44, Issue 5, Page(s) 1885–1894

Abstract: Background/aim: Breast cancer is a leading cause of cancer-related deaths among women. Down-regulation of the tumor suppressor gene Cyld in breast cancer has been linked to a poor prognosis. This study investigated the role of Cyld in breast cancer ... ...

Abstract	Background/aim: Breast cancer is a leading cause of cancer-related deaths among women. Down-regulation of the tumor suppressor gene Cyld in breast cancer has been linked to a poor prognosis. This study investigated the role of Cyld in breast cancer using conditional mutant mouse models carrying a Cyld mutation, which inactivates the deubiquitinating activity of its protein product CYLD in mammary epithelial cells. Materials and methods: We examined the potential of CYLD inactivation to induce mammary tumors spontaneously or modify the susceptibility of mice to mammary tumorigenesis by DMBA treatment or ErbB2 over-expression. Results: CYLD inactivation significantly increased susceptibility to breast cancer induced by either DMBA treatment or ErbB2 over-expression. Moreover, while CYLD inactivation alone did not lead to spontaneous mammary tumorigenesis, it did contribute to the formation of multifocal hyperplastic lesions in virgin mice of predominantly FVB/NJ background. Conclusion: Our study demonstrates the tumor enhancing potential of CYLD inactivation in mammary tumorigenesis in vivo and establishes novel relevant mouse models that can be exploited for developing prognostic and therapeutic protocols.
MeSH term(s)	Animals ; Female ; Mice ; 9,10-Dimethyl-1,2-benzanthracene/toxicity ; Breast Neoplasms/pathology ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Cell Transformation, Neoplastic/pathology ; Deubiquitinating Enzyme CYLD/genetics ; Deubiquitinating Enzyme CYLD/metabolism ; Mammary Neoplasms, Experimental/pathology ; Mammary Neoplasms, Experimental/genetics ; Mutation ; Receptor, ErbB-2/genetics ; Receptor, ErbB-2/metabolism ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism
Chemical Substances	9,10-Dimethyl-1,2-benzanthracene (57-97-6) ; CYLD protein, mouse (EC 3.4.19.12) ; Deubiquitinating Enzyme CYLD (EC 3.4.19.12) ; Receptor, ErbB-2 (EC 2.7.10.1) ; Tumor Suppressor Proteins
Language	English
Publishing date	2024-04-25
Publishing country	Greece
Document type	Journal Article
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
DOI	10.21873/anticanres.16990
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1642: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article: Inactivation of Tumor Suppressor CYLD Inhibits Fibroblast Reprogramming to Pluripotency.

Bekas, Nikolaos / Samiotaki, Martina / Papathanasiou, Maria / Mokos, Panagiotis / Pseftogas, Athanasios / Xanthopoulos, Konstantinos / Thanos, Dimitris / Mosialos, George / Dafou, Dimitra

Cancers

2023 Volume 15, Issue 20

Abstract: ... ...

Abstract	CYLD
Language	English
Publishing date	2023-10-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15204997
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: The expression of tumor suppressor gene Cyld is upregulated by histone deacetylace inhibitors in human hepatocellular carcinoma cell lines.

Kotantaki, Panorea / Mosialos, George

Cell biochemistry and function

2016 Volume 34, Issue 7, Page(s) 465–468

Abstract: CYLD is a deubiquitinating enzyme that exerts a tumor suppressive function. Its downregulation or inactivation has been associated with the development of several types of malignancies including hepatocellular carcinoma (HCC). HCC cells display ... ...

Abstract	CYLD is a deubiquitinating enzyme that exerts a tumor suppressive function. Its downregulation or inactivation has been associated with the development of several types of malignancies including hepatocellular carcinoma (HCC). HCC cells display significantly lower Cyld expression compared to primary human hepatocytes, and Cyld downregulation can contribute to apoptotic resistance of HCC cells. Little is known about the mechanism of Cyld downregulation in human HCC cells. In the present study we explored the possible regulation of Cyld expression by histone deacetylases (HDACs) in human HCC cell lines. We demonstrated that the HDAC inhibitors suberoylanilide hydroxamic acid, sodium butyrate, and trichostatin A induced the upregulation of both mRNA and protein levels of CYLD in two different HCC cell lines, HepG2 and Huh7. Our results demonstrate the involvement of HDACs in the downregulation of Cyld expression in HCC cells and support and may improve the use of HDAC inhibitors for the treatment for HCC.
MeSH term(s)	Butyric Acid/pharmacology ; Carcinoma, Hepatocellular/genetics ; Cell Line, Tumor ; Deubiquitinating Enzyme CYLD ; Gene Expression Regulation, Neoplastic/drug effects ; Histone Deacetylase Inhibitors/pharmacology ; Humans ; Hydroxamic Acids/pharmacology ; Liver Neoplasms/genetics ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism ; Up-Regulation/drug effects
Chemical Substances	Histone Deacetylase Inhibitors ; Hydroxamic Acids ; Tumor Suppressor Proteins ; Butyric Acid (107-92-6) ; trichostatin A (3X2S926L3Z) ; vorinostat (58IFB293JI) ; CYLD protein, human (EC 3.4.19.12) ; Deubiquitinating Enzyme CYLD (EC 3.4.19.12)
Language	English
Publishing date	2016-10
Publishing country	England
Document type	Journal Article
ZDB-ID	283643-9
ISSN	1099-0844 ; 0263-6484
ISSN (online)	1099-0844
ISSN	0263-6484
DOI	10.1002/cbf.3212
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1994: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Activation of peroxisome proliferator-activated receptor gamma in mammary epithelial cells upregulates the expression of tumor suppressor Cyld to mediate growth inhibition and anti-inflammatory effects.

Pseftogas, Athanasios / Gonidas, Christos / Mosialos, George

The international journal of biochemistry & cell biology

2017 Volume 82, Page(s) 49–56

Abstract: Several studies have implicated the downregulation of the tumor suppressor Cyld expression in breast cancer development. However, the mechanisms that regulate Cyld expression in mammary epithelial cells are largely unknown. In order to investigate them, ... ...

Abstract	Several studies have implicated the downregulation of the tumor suppressor Cyld expression in breast cancer development. However, the mechanisms that regulate Cyld expression in mammary epithelial cells are largely unknown. In order to investigate them, a bioinformatic analysis of the promoter region of Cyld was performed and identified putative nuclear hormone receptor response elements that included peroxisome proliferator-activated receptor gamma (PPAR-γ)-responsive elements. In the present study, we showed that upon activation of the nuclear hormone receptor PPAR-γ by the agonist troglitazone (TZD), there was a significant increase in Cyld mRNA in human mammary epithelial cell lines. The effect of TZD could be attributed to the transactivation of the Cyld promoter as indicated by the upregulation of a luciferase reporter that was driven by the -1995 to +95 region of the human Cyld gene. Furthermore, the upregulation of Cyld expression by TZD was dependent on PPAR-γ since downregulation of PPAR-γ expression by RNAi compromised the induction of Cyld expression by TZD. CYLD induction mediated, at least in part, the TZD-mediated downregulation of tumor necrosis factor α (TNFα)-induced interleukin 8 (IL-8). In addition, downregulation of CYLD compromised the cytotoxic effects of TZD in immortalized mammary epithelial cells. Our results demonstrated that PPAR-γ is a novel regulator of Cyld transcription and identified CYLD as a mediator of the PPAR-γ-dependent anti-inflammatory and anti-proliferative activity in mammary epithelial cells, which underscores its potential to be used as a target for the development of breast cancer therapeutic approaches.
MeSH term(s)	Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Antineoplastic Agents/pharmacology ; Breast Neoplasms/drug therapy ; Breast Neoplasms/immunology ; Breast Neoplasms/metabolism ; Cell Line, Transformed ; Cell Line, Tumor ; Cell Survival/drug effects ; Chromans/pharmacology ; Computational Biology ; Deubiquitinating Enzyme CYLD ; Female ; Gene Expression Regulation/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Hypoglycemic Agents/pharmacology ; Mammary Glands, Human/drug effects ; Mammary Glands, Human/immunology ; Mammary Glands, Human/metabolism ; Neoplasm Proteins/agonists ; Neoplasm Proteins/antagonists & inhibitors ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; PPAR gamma/agonists ; PPAR gamma/antagonists & inhibitors ; PPAR gamma/genetics ; PPAR gamma/metabolism ; Promoter Regions, Genetic/drug effects ; RNA Interference ; RNA, Messenger/metabolism ; Response Elements/drug effects ; Thiazolidinediones/pharmacology ; Tumor Suppressor Proteins/agonists ; Tumor Suppressor Proteins/antagonists & inhibitors ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Antineoplastic Agents ; Chromans ; Hypoglycemic Agents ; Neoplasm Proteins ; PPAR gamma ; RNA, Messenger ; Thiazolidinediones ; Tumor Suppressor Proteins ; CYLD protein, human (EC 3.4.19.12) ; Deubiquitinating Enzyme CYLD (EC 3.4.19.12) ; troglitazone (I66ZZ0ZN0E)
Language	English
Publishing date	2017-01
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1228429-4
ISSN	1878-5875 ; 1357-2725
ISSN (online)	1878-5875
ISSN	1357-2725
DOI	10.1016/j.biocel.2016.11.011
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 431: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Functional analysis of the C. elegans cyld-1 gene reveals extensive similarity with its human homolog.

Hadweh, Paul / Chaitoglou, Iro / Gravato-Nobre, Maria Joao / Ligoxygakis, Petros / Mosialos, George / Hatzivassiliou, Eudoxia

PloS one

2018 Volume 13, Issue 2, Page(s) e0191864

Abstract: The human cylindromatosis tumor suppressor (HsCyld) has attracted extensive attention due to its association with the development of multiple types of cancer. HsCyld encodes a deubiquitinating enzyme (HsCYLD) with a broad range of functions that include ... ...

Abstract	The human cylindromatosis tumor suppressor (HsCyld) has attracted extensive attention due to its association with the development of multiple types of cancer. HsCyld encodes a deubiquitinating enzyme (HsCYLD) with a broad range of functions that include the regulation of several cell growth, differentiation and death pathways. HsCyld is an evolutionarily conserved gene. Homologs of HsCyld have been identified in simple model organisms such as Drosophila melanogaster and Caenorhabditis elegans (C. elegans) which offer extensive possibilities for functional analyses. In the present report we have investigated and compared the functional properties of HsCYLD and its C. elegans homolog (CeCYLD). As expected from the mammalian CYLD expression pattern, the CeCyld promoter is active in multiple tissues with certain gastrointestinal epithelia and neuronal cells showing the most prominent activity. CeCYLD is a functional deubiquitinating enzyme with similar specificity to HsCYLD towards K63- and M1-linked polyubiquiting chains. CeCYLD was capable of suppressing the TRAF2-mediated activation of NF-kappaB and AP1 similarly to HsCYLD. Finally, CeCYLD could suppress the induction of TNF-dependent gene expression in mammalian cells similarly to HsCYLD. Our results demonstrate extensively overlapping functions between the HsCYLD and CeCYLD, which establish the C. elegans protein as a valuable model for the elucidation of the complex activity of the human tumor suppressor protein.
MeSH term(s)	Amino Acid Sequence ; Animals ; Caenorhabditis elegans/genetics ; Genes, Helminth ; Humans ; Promoter Regions, Genetic ; Real-Time Polymerase Chain Reaction ; Sequence Homology, Amino Acid
Language	English
Publishing date	2018-02-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0191864
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: The LMP1 promoter can be transactivated directly by NF-kappaB.

Demetriades, Constantinos / Mosialos, George

Journal of virology

2009 Volume 83, Issue 10, Page(s) 5269–5277

Abstract: A bioinformatic analysis identified two putative NF-kappaB binding sites in the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) promoter. The ability of p65RelA to interact with the LMP1 promoter was shown by in vitro and in vivo assays. Using ... ...

Abstract	A bioinformatic analysis identified two putative NF-kappaB binding sites in the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) promoter. The ability of p65RelA to interact with the LMP1 promoter was shown by in vitro and in vivo assays. Using an EBV-transformed lymphoblastoid cell line as a reporter system for the activity of the +40/-328 LMP1 promoter region, the functional importance of NF-kappaB and other transcription factor binding sites was demonstrated. p65RelA could also induce LMP1 expression from the EBV genome in Daudi and P3HR1 Burkitt's lymphoma cell lines. Finally, it was shown that p65RelA could cooperate with EBNA2 or the aryl hydrocarbon receptor in the transactivation of the LMP1 promoter. Our study established the importance of NF-kappaB and several cis-acting elements in the regulation of the LMP1 promoter in a latency III environment and highlighted a complex interplay between NF-kappaB and other transcription factors in this process.
MeSH term(s)	Base Sequence ; Binding Sites ; Cell Line, Transformed ; Gene Expression Regulation, Viral ; Herpesvirus 4, Human/genetics ; Herpesvirus 4, Human/metabolism ; Humans ; Molecular Sequence Data ; Promoter Regions, Genetic ; Protein Binding ; Transcription Factor RelA/metabolism ; Transcriptional Activation ; Viral Matrix Proteins/genetics
Chemical Substances	EBV-associated membrane antigen, Epstein-Barr virus ; Transcription Factor RelA ; Viral Matrix Proteins
Language	English
Publishing date	2009-03-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.00097-09
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 609: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The PP4R1 subunit of protein phosphatase PP4 targets TRAF2 and TRAF6 to mediate inhibition of NF-κB activation.

Hadweh, Paul / Habelhah, Hasem / Kieff, Elliott / Mosialos, George / Hatzivassiliou, Eudoxia

Cellular signalling

2014 Volume 26, Issue 12, Page(s) 2730–2737

Abstract: TRAFs constitute a family of proteins that have been implicated in signal transduction by immunomodulatory cellular receptors and viral proteins. TRAF2 and TRAF6 have an E3-ubiquitin ligase activity, which is dependent on the integrity of their RING ... ...

Abstract	TRAFs constitute a family of proteins that have been implicated in signal transduction by immunomodulatory cellular receptors and viral proteins. TRAF2 and TRAF6 have an E3-ubiquitin ligase activity, which is dependent on the integrity of their RING finger domain and it has been associated with their ability to activate the NF-κB and AP1 signaling pathways. A yeast two-hybrid screen with TRAF2 as bait, identified the regulatory subunit PP4R1 of protein phosphatase PP4 as a TRAF2-interacting protein. The interaction of TRAF2 with PP4R1 depended on the integrity of the RING finger domain of TRAF2. PP4R1 could interact also with the TRAF2-related factor TRAF6 in a RING domain-dependent manner. Exogenous expression of PP4R1 inhibited NF-κB activation by TRAF2, TRAF6, TNF and the Epstein-Barr virus oncoprotein LMP1. In addition, expression of PP4R1 downregulated IL8 induction by LMP1, whereas downregulation of PP4R1 by RNA interference enhanced the induction of IL8 by LMP1 and TNF. PP4R1 could mediate the dephosphorylation of TRAF2 Ser11, which has been previously implicated in TRAF2-mediated activation of NF-κB. Finally, PP4R1 could inhibit TRAF6 polyubiquitination, suggesting an interference with the E3 ubiquitin ligase activity of TRAF6. Taken together, our data identify a novel mechanism of NF-κB pathway inhibition which is mediated by PP4R1-dependent targeting of specific TRAF molecules.
MeSH term(s)	Down-Regulation/physiology ; HEK293 Cells ; Humans ; Interleukin-8/metabolism ; NF-kappa B/metabolism ; Phosphoprotein Phosphatases/metabolism ; RING Finger Domains/physiology ; Signal Transduction/physiology ; TNF Receptor-Associated Factor 2/metabolism ; TNF Receptor-Associated Factor 6/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination/physiology ; Viral Matrix Proteins
Chemical Substances	CXCL8 protein, human ; EBV-associated membrane antigen, Epstein-Barr virus ; Interleukin-8 ; NF-kappa B ; TNF Receptor-Associated Factor 2 ; TNF Receptor-Associated Factor 6 ; Viral Matrix Proteins ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Phosphoprotein Phosphatases (EC 3.1.3.16) ; protein phosphatase 4 (EC 3.1.3.16)
Language	English
Publishing date	2014-08-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1002702-6
ISSN	1873-3913 ; 0898-6568
ISSN (online)	1873-3913
ISSN	0898-6568
DOI	10.1016/j.cellsig.2014.08.001
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2579: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Truncation of the deubiquitinating domain of CYLD in myelomonocytic cells attenuates inflammatory responses.

Tsagaratou, Ageliki / Kontoyiannis, Dimitris L / Mosialos, George

PloS one

2011 Volume 6, Issue 1, Page(s) e16397

Abstract: The cylindromatosis tumor suppressor (CYLD) is a deubiquitinating enzyme that has been implicated in various aspects of adaptive and innate immune responses. Nevertheless, the role of CYLD in the function of specific types of immune cells remains elusive. ...

Abstract	The cylindromatosis tumor suppressor (CYLD) is a deubiquitinating enzyme that has been implicated in various aspects of adaptive and innate immune responses. Nevertheless, the role of CYLD in the function of specific types of immune cells remains elusive. In this report we have used conditional gene targeting in mice to address the role of the deubiquitinating activity of CYLD in the myelomonocytic lineage. Truncation of the deubiquitinating domain of CYLD specifically in myelomonocytic cells impaired the development of lethal LPS-induced endotoxic shock and the accumulation of thioglycollate-elicited peritoneal macrophages. Our data establish CYLD as a regulator of monocyte-macrophage activation in response to inflammatory stimuli and identify it as a potential target for therapeutic intervention in relevant inflammatory disorders in humans.
MeSH term(s)	Animals ; Cysteine Endopeptidases ; Deubiquitinating Enzyme CYLD ; Immunity ; Inflammation/prevention & control ; Leukemia, Myelomonocytic, Chronic/enzymology ; Lipopolysaccharides/pharmacology ; Macrophage Activation ; Macrophages, Peritoneal ; Mice ; Monocytes ; Shock, Septic/prevention & control ; Ubiquitination
Chemical Substances	Lipopolysaccharides ; CYLD protein, mouse (EC 3.4.19.12) ; Deubiquitinating Enzyme CYLD (EC 3.4.19.12) ; Cysteine Endopeptidases (EC 3.4.22.-)
Language	English
Publishing date	2011-01-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0016397
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: HDAC1/2 Inhibitor Romidepsin Suppresses DEN-Induced Hepatocellular Carcinogenesis in Mice.

Afaloniati, Hara / Angelopoulou, Katerina / Giakoustidis, Alexander / Hardas, Alexandros / Pseftogas, Athanasios / Makedou, Kali / Gargavanis, Athanasios / Goulopoulos, Thomas / Iliadis, Stavros / Papadopoulos, Vasileios / Papalois, Apostolos / Mosialos, George / Poutahidis, Theofilos / Giakoustidis, Dimitrios

OncoTargets and therapy

2020 Volume 13, Page(s) 5575–5588

Abstract: Background: Hepatocellular carcinoma (HCC) is a frequently diagnosed cancer and a leading cause of cancer-related death worldwide. Its rapid progression, combined with the limited treatment options at late stages, imposes the need for early detection ... ...

Abstract	Background: Hepatocellular carcinoma (HCC) is a frequently diagnosed cancer and a leading cause of cancer-related death worldwide. Its rapid progression, combined with the limited treatment options at late stages, imposes the need for early detection and aggressive intervention. Based on the knowledge that hepatocarcinogenesis is significantly influenced by histone acetylation, we directed our search for novel HCC therapeutics among histone deacetylation inhibitors (HDACi). The aim of the present study was to investigate the effect of HDAC1/2 inhibitor Romidepsin in the well-established mouse model of diethylnitrosamine (DEN)-induced HCC. Materials and methods: C56BL/6 mice were treated with Romidepsin at the critical point of 10 months after DEN challenge and their livers were examined 2 months later using histopathology and morphometry. Protein levels were assessed in serum using ELISA and in liver tissues using Western blot and immunohistochemistry (in-situ detection). Gene expression was quantified using real-time PCR. Results: Romidepsin suppressed cancer progression. This effect was associated with decreased proliferation and increased apoptosis of cancer cells. The cell cycle regulator Conclusion: These findings suggest that Romidepsin, a drug currently used in the treatment of lymphoma, could also be considered in the management of early-stage HCC.
Language	English
Publishing date	2020-06-15
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2495130-4
ISSN	1178-6930
ISSN	1178-6930
DOI	10.2147/OTT.S250233
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: The Tumor Suppressor CYLD Inhibits Mammary Epithelial to Mesenchymal Transition by the Coordinated Inhibition of YAP/TAZ and TGF Signaling.

Pseftogas, Athanasios / Xanthopoulos, Konstantinos / Poutahidis, Theofilos / Ainali, Chrysanthi / Dafou, Dimitra / Panteris, Emmanuel / Kern, Joseph G / Varelas, Xaralabos / Hardas, Alexander / Gonidas, Christos / Tsingotjidou, Anastasia / Hatzivassiliou, Eudoxia / Mosialos, George

Cancers

2020 Volume 12, Issue 8

Abstract: Downregulation of the cylindromatosis (CYLD) tumor suppressor has been associated with breast cancer development and progression. Here, we report a critical role for CYLD in maintaining the phenotype of mammary epithelial cells in vitro and in vivo. CYLD ...

Abstract	Downregulation of the cylindromatosis (CYLD) tumor suppressor has been associated with breast cancer development and progression. Here, we report a critical role for CYLD in maintaining the phenotype of mammary epithelial cells in vitro and in vivo. CYLD downregulation or inactivation induced an epithelial to mesenchymal transition of mammary epithelial cells that was dependent on the concomitant activation of the transcription factors Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) and transforming growth factor beta (TGF)signaling. CYLD inactivation enhanced the nuclear localization of YAP/TAZ and the phosphorylation of Small Mothers Against Decapentaplegic (SMAD)2/3 proteins in confluent cell culture conditions. Consistent with these findings were the hyperplastic alterations of CYLD-deficient mouse mammary epithelia, which were associated with enhanced nuclear expression of the YAP/TAZ transcription factors. Furthermore, in human breast cancer samples, downregulation of CYLD expression correlates with enhanced YAP/TAZ-regulated target gene expression. Our results identify CYLD as a critical regulator of a signaling node that prevents the coordinated activation of YAP/TAZ and the TGF pathway in mammary epithelial cells, in order to maintain their phenotypic identity and homeostasis. Consequently, they provide a novel conceptual framework that supports and explains a causal implication of deficient CYLD expression in aggressive human breast cancers.
Language	English
Publishing date	2020-07-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12082047
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito