LIVIVO - Search results -

Search results

Result 1 - 8 of total 8

Search options

Article: Neuregulin 1 expression is a predictive biomarker for response to AV-203, an ERBB3 inhibitory antibody, in human tumor models.

Meetze, Kristan / Vincent, Sylvie / Tyler, Steven / Mazsa, Elizabeth K / Delpero, Andrea R / Bottega, Steve / McIntosh, Donna / Nicoletti, Richard / Winston, William M / Weiler, Solly / Feng, Bin / Gyuris, Jeno / Weng, Zhigang

Clinical cancer research : an official journal of the American Association for Cancer Research

2015 Volume 21, Issue 5, Page(s) 1106–1114

Abstract: Purpose: ERBB3 is overexpressed in a broad spectrum of human cancers, and its aberrant activation is associated with tumor pathogenesis and therapeutic resistance to various anticancer agents. Neuregulin 1 (NRG1) is the predominant ligand for ERBB3 and ... ...

Abstract	Purpose: ERBB3 is overexpressed in a broad spectrum of human cancers, and its aberrant activation is associated with tumor pathogenesis and therapeutic resistance to various anticancer agents. Neuregulin 1 (NRG1) is the predominant ligand for ERBB3 and can promote the heterodimerization of ERBB3 with other ERBB family members, resulting in activation of multiple intracellular signaling pathways. AV-203 is a humanized IgG1/κ ERBB3 inhibitory antibody that completed a first-in-human phase I clinical trial in patients with advanced solid tumors. The purpose of this preclinical study was to identify potential biomarker(s) that may predict response to AV-203 treatment in the clinic. Experimental design: We conducted in vivo efficacy studies using a broad panel of xenograft models representing a wide variety of human cancers. To identify biomarkers that can predict response to AV-203, the relationship between tumor growth inhibition (TGI) by AV-203 and the expression levels of ERBB3 and NRG1 were evaluated in these tumor models. Results: A significant correlation was observed between the levels of NRG1 expression and TGI by AV-203. In contrast, TGI was not correlated with ERBB3 expression. The correlation between the levels of NRG1 expression in tumors and their response to ERBB3 inhibition by AV-203 was further validated using patient-derived tumor explant models. Conclusions: NRG1 is a promising biomarker that can predict response to ERBB3 inhibition by AV-203 in preclinical human cancer models. NRG1 warrants further clinical evaluation and validation as a potential predictive biomarker of response to AV-203.
MeSH term(s)	Animals ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antibodies, Monoclonal, Humanized/pharmacology ; Area Under Curve ; Biomarkers ; Cell Line, Tumor ; Disease Models, Animal ; Drug Resistance, Neoplasm/genetics ; Female ; Gene Expression ; Humans ; Ligands ; Mice ; Mutation ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Neuregulin-1/genetics ; Neuregulin-1/metabolism ; Prognosis ; Protein Binding ; Receptor, ErbB-3/antagonists & inhibitors ; Receptor, ErbB-3/genetics ; Receptor, ErbB-3/metabolism ; Reproducibility of Results ; Xenograft Model Antitumor Assays
Chemical Substances	AV-203 ; Antibodies, Monoclonal, Humanized ; Biomarkers ; Ligands ; Neuregulin-1 ; Receptor, ErbB-3 (EC 2.7.10.1)
Language	English
Publishing date	2015-03-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-14-2407
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4223: 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

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 ; Online: Genomic discovery of an evolutionarily programmed modality for small-molecule targeting of an intractable protein surface.

Shigdel, Uddhav K / Lee, Seung-Joo / Sowa, Mathew E / Bowman, Brian R / Robison, Keith / Zhou, Minyun / Pua, Khian Hong / Stiles, Dylan T / Blodgett, Joshua A V / Udwary, Daniel W / Rajczewski, Andrew T / Mann, Alan S / Mostafavi, Siavash / Hardy, Tara / Arya, Sukrat / Weng, Zhigang / Stewart, Michelle / Kenyon, Kyle / Morgenstern, Jay P /

Pan, Ende / Gray, Daniel C / Pollock, Roy M / Fry, Andrew M / Klausner, Richard D / Townson, Sharon A / Verdine, Gregory L

Proceedings of the National Academy of Sciences of the United States of America

2020 Volume 117, Issue 29, Page(s) 17195–17203

Abstract: The vast majority of intracellular protein targets are refractory toward small-molecule therapeutic engagement, and additional therapeutic modalities are needed to overcome this deficiency. Here, the identification and characterization of a natural ... ...

Abstract	The vast majority of intracellular protein targets are refractory toward small-molecule therapeutic engagement, and additional therapeutic modalities are needed to overcome this deficiency. Here, the identification and characterization of a natural product, WDB002, reveals a therapeutic modality that dramatically expands the currently accepted limits of druggability. WDB002, in complex with the FK506-binding protein (FKBP12), potently and selectively binds the human centrosomal protein 250 (CEP250), resulting in disruption of CEP250 function in cells. The recognition mode is unprecedented in that the targeted domain of CEP250 is a coiled coil and is topologically featureless, embodying both a structural motif and surface topology previously considered on the extreme limits of "undruggability" for an intracellular target. Structural studies reveal extensive protein-WDB002 and protein-protein contacts, with the latter being distinct from those seen in FKBP12 ternary complexes formed by FK506 and rapamycin. Outward-facing structural changes in a bound small molecule can thus reprogram FKBP12 to engage diverse, otherwise "undruggable" targets. The flat-targeting modality demonstrated here has the potential to expand the druggable target range of small-molecule therapeutics. As CEP250 was recently found to be an interaction partner with the Nsp13 protein of the SARS-CoV-2 virus that causes COVID-19 disease, it is possible that WDB002 or an analog may exert useful antiviral activity through its ability to form high-affinity ternary complexes containing CEP250 and FKBP12.
MeSH term(s)	Actinobacteria/genetics ; Actinobacteria/metabolism ; Amino Acid Sequence ; Antiviral Agents/chemistry ; Antiviral Agents/metabolism ; Antiviral Agents/pharmacology ; Autoantigens/genetics ; Autoantigens/metabolism ; Calcineurin/genetics ; Calcineurin/metabolism ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Evolution, Molecular ; Genome, Bacterial ; HEK293 Cells ; Humans ; Macrolides/chemistry ; Macrolides/metabolism ; Macrolides/pharmacology ; Models, Molecular ; Protein Conformation ; Protein Interaction Domains and Motifs/drug effects ; Sequence Homology ; Sirolimus/chemistry ; Sirolimus/metabolism ; Small Molecule Libraries/chemistry ; Small Molecule Libraries/metabolism ; Small Molecule Libraries/pharmacology ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; Tacrolimus Binding Protein 1A/chemistry ; Tacrolimus Binding Protein 1A/metabolism
Chemical Substances	Antiviral Agents ; Autoantigens ; Cell Cycle Proteins ; CEP250 protein, human ; Macrolides ; Small Molecule Libraries ; WDB002 ; MTOR protein, human (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; Calcineurin (EC 3.1.3.16) ; Tacrolimus Binding Protein 1A (EC 5.2.1.-) ; Sirolimus (W36ZG6FT64)
Keywords	covid19
Language	English
Publishing date	2020-06-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2006560117
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1148: 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: MAP3K11/GDF15 axis is a critical driver of cancer cachexia.

Lerner, Lorena / Tao, Julie / Liu, Qing / Nicoletti, Richard / Feng, Bin / Krieger, Brian / Mazsa, Elizabeth / Siddiquee, Zakir / Wang, Ruoji / Huang, Lucia / Shen, Luhua / Lin, Jie / Vigano, Antonio / Chiu, M Isabel / Weng, Zhigang / Winston, William / Weiler, Solly / Gyuris, Jeno

Journal of cachexia, sarcopenia and muscle

2015 Volume 7, Issue 4, Page(s) 467–482

Abstract: Background: Cancer associated cachexia affects the majority of cancer patients during the course of the disease and thought to be directly responsible for about a quarter of all cancer deaths. Current evidence suggests that a pro-inflammatory state may ... ...

Abstract	Background: Cancer associated cachexia affects the majority of cancer patients during the course of the disease and thought to be directly responsible for about a quarter of all cancer deaths. Current evidence suggests that a pro-inflammatory state may be associated with this syndrome although the molecular mechanisms responsible for the development of cachexia are poorly understood. The purpose of this work was the identification of key drivers of cancer cachexia that could provide a potential point of intervention for the treatment and/or prevention of this syndrome. Methods: Genetically engineered and xenograft tumour models were used to dissect the molecular mechanisms driving cancer cachexia. Cytokine profiling from the plasma of cachectic and non-cachectic cancer patients and mouse models was utilized to correlate circulating cytokine levels with the cachexia phenotype. Results: Utilizing engineered tumour models we identified MAP3K11/GDF15 pathway activation as a potent inducer of cancer cachexia. Increased expression and high circulating levels of GDF15 acted as a key mediator of this process. In animal models, tumour-produced GDF15 was sufficient to trigger the cachexia phenotype. Elevated GDF15 circulating levels correlated with the onset and progression of cachexia in animal models and in patients with cancer. Inhibition of GDF15 biological activity with a specific antibody reversed body weight loss and restored muscle and fat tissue mass in several cachectic animal models regardless of their complex secreted cytokine profile. Conclusions: The combination of correlative observations, gain of function, and loss of function experiments validated GDF15 as a key driver of cancer cachexia and as a potential therapeutic target for the treatment and/or prevention of this syndrome.
Language	English
Publishing date	2015-10-29
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2586864-0
ISSN	2190-6009 ; 2190-5991
ISSN (online)	2190-6009
ISSN	2190-5991
DOI	10.1002/jcsm.12077
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: A functional screen in human cells identifies UBF2 as an RNA polymerase II transcription factor that enhances the beta-catenin signaling pathway.

Grueneberg, Dorre A / Pablo, Lourdes / Hu, Kang-Quan / August, Paul / Weng, Zhigang / Papkoff, Jacqueline

Molecular and cellular biology

2003 Volume 23, Issue 11, Page(s) 3936–3950

Abstract: beta-Catenin signaling plays an important role in the development of many organisms and has a key part in driving the malignant transformation of epithelial cells comprising a variety of cancers. beta-Catenin can activate gene expression through its ... ...

Abstract	beta-Catenin signaling plays an important role in the development of many organisms and has a key part in driving the malignant transformation of epithelial cells comprising a variety of cancers. beta-Catenin can activate gene expression through its association with transcription factors of the lymphoid enhancer factor 1 (LEF-1)/T-cell factor (TCF) family. We designed a screen in human cells to identify novel genes that activate a beta-catenin-LEF/TCF-responsive promoter and isolated the high-mobility group box transcription factor, UBF2. UBF1 and UBF2 are splice variants of a common precursor RNA. Although UBF1 has been shown to activate RNA polymerase I-regulated genes, the function of UBF2 has remained obscure. Here, we show for the first time that both UBF1 and UBF2 activate RNA polymerase II-regulated promoters. UBF2 associates with LEF-1, as shown by coimmunoprecipitation experiments, and potentiates transcriptional activation stimulated by LEF-1/beta-catenin from a synthetic promoter with multimerized LEF/TCF binding sites and a natural cyclin D1 promoter with consensus LEF/TCF binding sites. Downregulation of endogenous UBF expression using an RNA interference approach reduces transcriptional activation of a beta-catenin-LEF/TCF-responsive promoter by means of overexpressed beta-catenin, further implicating UBF as a transcriptional enhancer of the beta-catenin pathway.
MeSH term(s)	Amino Acid Sequence ; Cell Line ; Cell Nucleus/metabolism ; Cyclin D1/genetics ; Cyclin D1/metabolism ; Cytoskeletal Proteins/genetics ; Cytoskeletal Proteins/metabolism ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Genes, Reporter ; High Mobility Group Proteins/chemistry ; High Mobility Group Proteins/genetics ; High Mobility Group Proteins/metabolism ; Humans ; Lymphoid Enhancer-Binding Factor 1 ; Molecular Sequence Data ; Pol1 Transcription Initiation Complex Proteins/chemistry ; Pol1 Transcription Initiation Complex Proteins/genetics ; Pol1 Transcription Initiation Complex Proteins/metabolism ; Promoter Regions, Genetic ; RNA Polymerase II/metabolism ; Recombinant Fusion Proteins/metabolism ; Sequence Alignment ; Signal Transduction/physiology ; Trans-Activators/genetics ; Trans-Activators/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; beta Catenin
Chemical Substances	CTNNB1 protein, human ; Cytoskeletal Proteins ; DNA-Binding Proteins ; High Mobility Group Proteins ; LEF1 protein, human ; Lymphoid Enhancer-Binding Factor 1 ; Pol1 Transcription Initiation Complex Proteins ; Recombinant Fusion Proteins ; Trans-Activators ; Transcription Factors ; beta Catenin ; transcription factor UBF ; Cyclin D1 (136601-57-5) ; RNA Polymerase II (EC 2.7.7.-)
Language	English
Publishing date	2003-05-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	779397-2
ISSN	1098-5549 ; 0270-7306
ISSN (online)	1098-5549
ISSN	0270-7306
DOI	10.1128/MCB.23.11.3936-3950.2003
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1666: 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: Genomic discovery of an evolutionarily programmed modality for small-molecule targeting of an intractable protein surface

Pan, Ende / Gray, Daniel C / Pollock, Roy M / Fry, Andrew M / Klausner, Richard D / Townson, Sharon A / Verdine, Gregory L

Proc Natl Acad Sci U S A

Abstract	The vast majority of intracellular protein targets are refractory toward small-molecule therapeutic engagement, and additional therapeutic modalities are needed to overcome this deficiency. Here, the identification and characterization of a natural product, WDB002, reveals a therapeutic modality that dramatically expands the currently accepted limits of druggability. WDB002, in complex with the FK506-binding protein (FKBP12), potently and selectively binds the human centrosomal protein 250 (CEP250), resulting in disruption of CEP250 function in cells. The recognition mode is unprecedented in that the targeted domain of CEP250 is a coiled coil and is topologically featureless, embodying both a structural motif and surface topology previously considered on the extreme limits of "undruggability" for an intracellular target. Structural studies reveal extensive protein-WDB002 and protein-protein contacts, with the latter being distinct from those seen in FKBP12 ternary complexes formed by FK506 and rapamycin. Outward-facing structural changes in a bound small molecule can thus reprogram FKBP12 to engage diverse, otherwise "undruggable" targets. The flat-targeting modality demonstrated here has the potential to expand the druggable target range of small-molecule therapeutics. As CEP250 was recently found to be an interaction partner with the Nsp13 protein of the SARS-CoV-2 virus that causes COVID-19 disease, it is possible that WDB002 or an analog may exert useful antiviral activity through its ability to form high-affinity ternary complexes containing CEP250 and FKBP12.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #624792
Database	COVID19

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.

Details ▾

Article ; Online: Genomic discovery of an evolutionarily programmed modality for small-molecule targeting of an intractable protein surface.

Shigdel, Uddhav K / Lee, Seung-Joo / Sowa, Mathew E / Bowman, Brian R / Robison, Keith / Zhou, Minyun / Pua, Khian Hong / Stiles, Dylan T / Blodgett, Joshua AV / Udwary, Daniel W / Rajczewski, Andrew T / Mann, Alan S / Mostafavi, Siavash / Hardy, Tara / Arya, Sukrat / Weng, Zhigang / Stewart, Michelle / Kenyon, Kyle / Morgenstern, Jay P /

Pan, Ende / Gray, Daniel C / Pollock, Roy M / Fry, Andrew M / Klausner, Richard D / Townson, Sharon A / Verdine, Gregory L

Proceedings of the National Academy of Sciences of the United States of America, vol 117, iss 29

2020

Abstract	The vast majority of intracellular protein targets are refractory toward small-molecule therapeutic engagement, and additional therapeutic modalities are needed to overcome this deficiency. Here, the identification and characterization of a natural product, WDB002, reveals a therapeutic modality that dramatically expands the currently accepted limits of druggability. WDB002, in complex with the FK506-binding protein (FKBP12), potently and selectively binds the human centrosomal protein 250 (CEP250), resulting in disruption of CEP250 function in cells. The recognition mode is unprecedented in that the targeted domain of CEP250 is a coiled coil and is topologically featureless, embodying both a structural motif and surface topology previously considered on the extreme limits of "undruggability" for an intracellular target. Structural studies reveal extensive protein-WDB002 and protein-protein contacts, with the latter being distinct from those seen in FKBP12 ternary complexes formed by FK506 and rapamycin. Outward-facing structural changes in a bound small molecule can thus reprogram FKBP12 to engage diverse, otherwise "undruggable" targets. The flat-targeting modality demonstrated here has the potential to expand the druggable target range of small-molecule therapeutics. As CEP250 was recently found to be an interaction partner with the Nsp13 protein of the SARS-CoV-2 virus that causes COVID-19 disease, it is possible that WDB002 or an analog may exert useful antiviral activity through its ability to form high-affinity ternary complexes containing CEP250 and FKBP12.
Keywords	Humans ; Actinobacteria ; Sirolimus ; Calcineurin ; Tacrolimus Binding Protein 1A ; Cell Cycle Proteins ; Autoantigens ; Anti-Bacterial Agents ; Evolution ; Molecular ; Amino Acid Sequence ; Protein Conformation ; Sequence Homology ; Genome ; Bacterial ; Models ; Protein Interaction Domains and Motifs ; Small Molecule Libraries ; HEK293 Cells ; TOR Serine-Threonine Kinases ; FK506-binding protein ; genome mining ; natural products ; covid19
Subject code	612
Publishing date	2020-07-01
Publisher	eScholarship, University of California
Publishing country	us
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

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 ; Online: GP369, an FGFR2-IIIb-specific antibody, exhibits potent antitumor activity against human cancers driven by activated FGFR2 signaling.

Bai, Ailin / Meetze, Kristan / Vo, Nhi Y / Kollipara, Sriram / Mazsa, Elizabeth K / Winston, William M / Weiler, Solly / Poling, Laura L / Chen, Ting / Ismail, Nesreen S / Jiang, Jinwei / Lerner, Lorena / Gyuris, Jeno / Weng, Zhigang

Cancer research

2010 Volume 70, Issue 19, Page(s) 7630–7639

Abstract: Dysregulated fibroblast growth factor (FGF) signaling has been implicated in the pathogenesis of human cancers. Aberrant activation of FGF receptor 2 (FGFR2) signaling, through overexpression of FGFR2 and/or its ligands, mutations, and receptor ... ...

Abstract	Dysregulated fibroblast growth factor (FGF) signaling has been implicated in the pathogenesis of human cancers. Aberrant activation of FGF receptor 2 (FGFR2) signaling, through overexpression of FGFR2 and/or its ligands, mutations, and receptor amplification, has been found in a variety of human tumors. We generated monoclonal antibodies against the extracellular ligand-binding domain of FGFR2 to address the role of FGFR2 in tumorigenesis and to explore the potential of FGFR2 as a novel therapeutic target. We surveyed a broad panel of human cancer cell lines for the dysregulation of FGFR2 signaling and discovered that breast and gastric cancer cell lines harboring FGFR2 amplification predominantly express the IIIb isoform of the receptor. Therefore, we used an FGFR2-IIIb-specific antibody, GP369, to investigate the importance of FGFR2 signaling in vitro and in vivo. GP369 specifically and potently suppressed ligand-induced phosphorylation of FGFR2-IIIb and downstream signaling, as well as FGFR2-driven proliferation in vitro. The administration of GP369 in mice significantly inhibited the growth of human cancer xenografts harboring activated FGFR2 signaling. Our findings support the hypothesis that dysregulated FGFR2 signaling is one of the critical oncogenic pathways involved in the initiation and/or maintenance of tumors. Cancer patients with aberrantly activated/amplified FGFR2 signaling could potentially benefit from therapeutic intervention with FGFR2-targeting antibodies.
MeSH term(s)	Amino Acid Sequence ; Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/pharmacology ; Antibody Specificity ; Cell Growth Processes/drug effects ; Cell Line, Tumor ; Female ; Gene Amplification ; Humans ; Mice ; Mice, SCID ; Molecular Sequence Data ; Neoplasms/enzymology ; Neoplasms/genetics ; Neoplasms/immunology ; Neoplasms/therapy ; Phosphorylation/drug effects ; Receptor, Fibroblast Growth Factor, Type 2/antagonists & inhibitors ; Receptor, Fibroblast Growth Factor, Type 2/genetics ; Receptor, Fibroblast Growth Factor, Type 2/immunology ; Receptor, Fibroblast Growth Factor, Type 2/metabolism ; Signal Transduction ; Xenograft Model Antitumor Assays
Chemical Substances	Antibodies, Monoclonal ; FGFR2 protein, human (EC 2.7.10.1) ; Receptor, Fibroblast Growth Factor, Type 2 (EC 2.7.10.1) ; keratinocyte growth factor receptor (EC 2.7.10.1)
Language	English
Publishing date	2010-10-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-10-1489
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uh III Zs.135/5: Show issues

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

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Protection against anoikis and down-regulation of cadherin expression by a regulatable beta-catenin protein.

Weng, Zhigang / Xin, Mei / Pablo, Lourdes / Grueneberg, Dorre / Hagel, Margit / Bain, Gerard / Müller, Thomas / Papkoff, Jackie

The Journal of biological chemistry

2002 Volume 277, Issue 21, Page(s) 18677–18686

Abstract: beta-Catenin signaling plays a key role in a variety of cellular contexts during embryonic development and tissue differentiation. Aberrant beta-catenin signaling has also been implicated in promoting human colorectal carcinomas as well as a variety of ... ...

Abstract	beta-Catenin signaling plays a key role in a variety of cellular contexts during embryonic development and tissue differentiation. Aberrant beta-catenin signaling has also been implicated in promoting human colorectal carcinomas as well as a variety of other cancers. To study the molecular and cellular biological functions of beta-catenin in a controlled fashion, we created a regulatable form of activated beta-catenin by fusion to a modified estrogen receptor (ER) ligand binding domain (G525R). Transfection of tissue culture cells with expression vectors encoding this hybrid protein allows the signal transduction function of beta-catenin to be induced by the synthetic estrogen, 4-hydroxytamoxifen, leading to regulated activation of a beta-catenin-lymphocyte enhancer-binding factor-dependent reporter gene as well as induction of endogenous cyclin D1 expression. The activation of ER-beta-catenin signaling rescues RK3E cells from anoikis and correlates with an increased phosphorylation of mitogen-activated protein kinase. The inhibition of anoikis by ER-beta-catenin can be abolished by a mitogen-activated protein kinase pathway inhibitor, PD98059. Evidence is also provided to show that ER-beta-catenin down-regulates cadherin protein levels. These findings support a key role for activated beta-catenin signaling in processes that contribute to tumor formation and progression.
MeSH term(s)	Animals ; Anoikis ; Cadherins/metabolism ; Cell Line ; Cytoskeletal Proteins/metabolism ; Cytoskeletal Proteins/physiology ; Dogs ; Down-Regulation/physiology ; Gene Expression Regulation/physiology ; Genes, Reporter ; MAP Kinase Signaling System ; Mutagenesis, Site-Directed ; Trans-Activators ; beta Catenin
Chemical Substances	Cadherins ; Cytoskeletal Proteins ; Trans-Activators ; beta Catenin
Language	English
Publishing date	2002-03-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M105331200
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.108: Show issues

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

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

Search results

Search options

Article: Neuregulin 1 expression is a predictive biomarker for response to AV-203, an ERBB3 inhibitory antibody, in human tumor models.

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Article ; Online: Genomic discovery of an evolutionarily programmed modality for small-molecule targeting of an intractable protein surface.

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Article: MAP3K11/GDF15 axis is a critical driver of cancer cachexia.

More links

Kategorien

Order via subito

Article: A functional screen in human cells identifies UBF2 as an RNA polymerase II transcription factor that enhances the beta-catenin signaling pathway.

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Article: Genomic discovery of an evolutionarily programmed modality for small-molecule targeting of an intractable protein surface

Kategorien

Inter-library loan at ZB MED

Article ; Online: Genomic discovery of an evolutionarily programmed modality for small-molecule targeting of an intractable protein surface.

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Article ; Online: GP369, an FGFR2-IIIb-specific antibody, exhibits potent antitumor activity against human cancers driven by activated FGFR2 signaling.

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Article: Protection against anoikis and down-regulation of cadherin expression by a regulatable beta-catenin protein.

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito