LIVIVO - Search results -

Search results

Result 1 - 10 of total 14

Search options

Article ; Online: CDK2 regulates collapsed replication fork repair in CCNE1-amplified ovarian cancer cells via homologous recombination.

Brown, Victoria E / Moore, Sydney L / Chen, Maxine / House, Nealia / Ramsden, Philip / Wu, Hsin-Jung / Ribich, Scott / Grassian, Alexandra R / Choi, Yoon Jong

NAR cancer

2023 Volume 5, Issue 3, Page(s) zcad039

Abstract: ... ...

Abstract	CCNE1
Language	English
Publishing date	2023-07-27
Publishing country	England
Document type	Journal Article
ISSN	2632-8674
ISSN (online)	2632-8674
DOI	10.1093/narcan/zcad039
Database	MEDical Literature Analysis and Retrieval System OnLINE

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.

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: Mutations of isocitrate dehydrogenase 1 and 2 in intrahepatic cholangiocarcinoma.

Grassian, Alexandra R / Pagliarini, Raymond / Chiang, Derek Y

Current opinion in gastroenterology

2014 Volume 30, Issue 3, Page(s) 295–302

Abstract: Purpose of review: Exome sequencing studies have recently expanded the genetic characterization of intrahepatic cholangiocarcinomas. Among a number of novel genes, isocitrate dehydrogenase (IDH) is recurrently mutated in intrahepatic cholangiocarcinomas. ...

Abstract	Purpose of review: Exome sequencing studies have recently expanded the genetic characterization of intrahepatic cholangiocarcinomas. Among a number of novel genes, isocitrate dehydrogenase (IDH) is recurrently mutated in intrahepatic cholangiocarcinomas. We review the effects of these mutations on several biochemical pathways, as well as potential changes to downstream signaling pathways. Recent findings: Hotspot mutations in IDH isoforms 1 or 2 occur in approximately 15% of intrahepatic cholangiocarcinomas. These mutations result in elevated levels of an oncometabolite, 2-hydroxyglutarate, which is associated with higher DNA CpG methylation and altered histone methylation that accompany a block in cellular differentiation. Exploratory studies have suggested additional phenotypes associated with IDH1/2 mutations. Summary: Tumors with IDH1 or IDH2 mutations may represent a distinct subtype of cholangiocarcinomas. Further studies are required to elucidate the exact role that mutant IDH1/2 and 2-hydroxyglutarate play in tumorigenesis, and what are the best strategies to target these tumor types.
MeSH term(s)	Bile Duct Neoplasms/genetics ; Bile Duct Neoplasms/pathology ; Bile Ducts, Intrahepatic ; Cell Differentiation/genetics ; Cholangiocarcinoma/genetics ; Cholangiocarcinoma/pathology ; DNA Methylation ; Glutarates/metabolism ; Humans ; Isocitrate Dehydrogenase/genetics ; Mutation ; Prolyl Hydroxylases/metabolism ; Signal Transduction/genetics
Chemical Substances	Glutarates ; alpha-hydroxyglutarate (2889-31-8) ; IDH2 protein, human (EC 1.1.1.41) ; Isocitrate Dehydrogenase (EC 1.1.1.41) ; IDH1 protein, human (EC 1.1.1.42.) ; Prolyl Hydroxylases (EC 1.14.11.-)
Language	English
Publishing date	2014-02-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	632571-3
ISSN	1531-7056 ; 0267-1379
ISSN (online)	1531-7056
ISSN	0267-1379
DOI	10.1097/MOG.0000000000000050
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2072: 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: ErbB2 stabilizes epidermal growth factor receptor (EGFR) expression via Erk and Sprouty2 in extracellular matrix-detached cells.

Grassian, Alexandra R / Schafer, Zachary T / Brugge, Joan S

The Journal of biological chemistry

2010 Volume 286, Issue 1, Page(s) 79–90

Abstract: Epithelial cells are dependent on extracellular matrix (ECM) attachment for maintenance of metabolic activity and suppression of apoptosis. Here we show that loss of ECM attachment causes down-regulation of epidermal growth factor receptor (EGFR) and β1 ... ...

Abstract	Epithelial cells are dependent on extracellular matrix (ECM) attachment for maintenance of metabolic activity and suppression of apoptosis. Here we show that loss of ECM attachment causes down-regulation of epidermal growth factor receptor (EGFR) and β1 integrin protein and mRNA expression and that ErbB2, which is amplified in 25% of breast tumors, reverses these effects of ECM deprivation. ErbB2 rescue of β1 integrin mRNA and protein in suspended cells is dependent on EGFR, however, the rescue of EGFR expression does not require β1 integrin. We show that there is a significant decrease in the stability of EGFR in ECM-detached cells that is reversed by ErbB2 overexpression. Rescue of both EGFR and β1 integrin protein by ErbB2 is dependent on Erk activity and induction of its downstream target Sprouty2, a protein known to regulate EGFR protein stability. Interestingly, expression of EGFR and β1 integrin protein is more dependent on Erk/Sprouty2 in ECM-detached ErbB2-overexpressing cells when compared with ECM-attached cells. These results provide further insight into the ErbB2-driven anchorage independence of tumor cells and provide a new mechanism for regulation of EGFR and β1 integrin expression in ECM-detached cells.
MeSH term(s)	Adenosine Triphosphate/metabolism ; Cell Line, Tumor ; Down-Regulation ; ErbB Receptors/chemistry ; ErbB Receptors/genetics ; ErbB Receptors/metabolism ; Extracellular Matrix/metabolism ; Extracellular Signal-Regulated MAP Kinases/genetics ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Gene Expression Regulation ; Humans ; Integrin beta Chains/metabolism ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Membrane Proteins ; Protein Stability ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Receptor, ErbB-2/metabolism
Chemical Substances	Integrin beta Chains ; Intracellular Signaling Peptides and Proteins ; Membrane Proteins ; RNA, Messenger ; SPRY2 protein, human ; Adenosine Triphosphate (8L70Q75FXE) ; ErbB Receptors (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24)
Language	English
Publishing date	2010-10-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M110.169821
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

Article: ErbB2 Stabilizes Epidermal Growth Factor Receptor (EGFR) Expression via Erk and Sprouty2 in Extracellular Matrix-detached Cells

Grassian, Alexandra R / Schafer, Zachary T / Brugge, Joan S

Journal of biological chemistry. 2011 Jan. 7, v. 286, no. 1

2011

Abstract	Epithelial cells are dependent on extracellular matrix (ECM) attachment for maintenance of metabolic activity and suppression of apoptosis. Here we show that loss of ECM attachment causes down-regulation of epidermal growth factor receptor (EGFR) and β1 integrin protein and mRNA expression and that ErbB2, which is amplified in 25% of breast tumors, reverses these effects of ECM deprivation. ErbB2 rescue of β1 integrin mRNA and protein in suspended cells is dependent on EGFR, however, the rescue of EGFR expression does not require β1 integrin. We show that there is a significant decrease in the stability of EGFR in ECM-detached cells that is reversed by ErbB2 overexpression. Rescue of both EGFR and β1 integrin protein by ErbB2 is dependent on Erk activity and induction of its downstream target Sprouty2, a protein known to regulate EGFR protein stability. Interestingly, expression of EGFR and β1 integrin protein is more dependent on Erk/Sprouty2 in ECM-detached ErbB2-overexpressing cells when compared with ECM-attached cells. These results provide further insight into the ErbB2-driven anchorage independence of tumor cells and provide a new mechanism for regulation of EGFR and β1 integrin expression in ECM-detached cells.
Language	English
Dates of publication	2011-0107
Size	p. 79-90.
Publishing place	American Society for Biochemistry and Molecular Biology
Document type	Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Bonn / Germany

Z 4' 65/118: Show issues
Z 6.2: Show issues

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.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Erk regulation of pyruvate dehydrogenase flux through PDK4 modulates cell proliferation.

Grassian, Alexandra R / Metallo, Christian M / Coloff, Jonathan L / Stephanopoulos, Gregory / Brugge, Joan S

Genes & development

2011 Volume 25, Issue 16, Page(s) 1716–1733

Abstract: Loss of extracellular matrix (ECM) attachment leads to metabolic impairments that limit cellular energy production. Characterization of the metabolic alterations induced by ECM detachment revealed a dramatic decrease in uptake of glucose, glutamine, and ... ...

Abstract	Loss of extracellular matrix (ECM) attachment leads to metabolic impairments that limit cellular energy production. Characterization of the metabolic alterations induced by ECM detachment revealed a dramatic decrease in uptake of glucose, glutamine, and pyruvate, and a consequent decrease in flux through glycolysis, the pentose phosphate pathway, and the tricarboxylic acid (TCA) cycle. However, flux through pyruvate dehydrogenase (PDH) is disproportionally decreased, concomitant with increased expression of the PDH inhibitory kinase, PDH kinase 4 (PDK4), and increased carbon secretion. Overexpression of ErbB2 maintains PDH flux by suppressing PDK4 expression in an Erk-dependent manner, and Erk signaling also regulates PDH flux in ECM-attached cells. Additionally, epidermal growth factor (EGF), a potent inducer of Erk, positively regulates PDH flux through decreased PDK4 expression. Furthermore, overexpression of PDK4 in ECM-detached cells suppresses the ErbB2-mediated rescue of ATP levels, and in attached cells, PDK4 overexpression decreases PDH flux, de novo lipogenesis, and cell proliferation. Mining of microarray data from human tumor data sets revealed that PDK4 mRNA is commonly down-regulated in tumors compared with their tissues of origin. These results identify a novel mechanism by which ECM attachment, growth factors, and oncogenes modulate the metabolic fate of glucose by controlling PDK4 expression and PDH flux to influence proliferation.
MeSH term(s)	Adenosine Triphosphate/metabolism ; Animals ; Cell Adhesion ; Cell Line ; Cell Proliferation ; Citric Acid Cycle ; Epidermal Growth Factor/pharmacology ; Extracellular Matrix/metabolism ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Glucose/metabolism ; Humans ; Immunoblotting ; Insulin/pharmacology ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Phosphorylation/drug effects ; Protein Kinases/genetics ; Protein Kinases/metabolism ; Pyruvate Dehydrogenase Complex/metabolism ; Pyruvic Acid/metabolism ; Receptor, ErbB-2/genetics ; Receptor, ErbB-2/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/drug effects
Chemical Substances	Insulin ; Pyruvate Dehydrogenase Complex ; Epidermal Growth Factor (62229-50-9) ; Pyruvic Acid (8558G7RUTR) ; Adenosine Triphosphate (8L70Q75FXE) ; Protein Kinases (EC 2.7.-) ; pyruvate dehydrogenase kinase 4 (EC 2.7.1.-) ; Receptor, ErbB-2 (EC 2.7.10.1) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase 1 (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase 3 (EC 2.7.11.24) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2011-08-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	806684-x
ISSN	1549-5477 ; 0890-9369
ISSN (online)	1549-5477
ISSN	0890-9369
DOI	10.1101/gad.16771811
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2292: 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)
Zs.MG 54: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Correction: Preclinical Evidence of Anti-Tumor Activity Induced by EZH2 Inhibition in Human Models of Synovial Sarcoma.

Kawano, Satoshi / Grassian, Alexandra R / Tsuda, Masumi / Knutson, Sarah K / Warholic, Natalie M / Kuznetsov, Galina / Xu, Shanqin / Xiao, Yonghong / Pollock, Roy M / Smith, Jesse J / Kuntz, Kevin W / Ribich, Scott / Minoshima, Yukinori / Matsui, Junji / Copeland, Robert A / Tanaka, Shinya / Keilhack, Heike

PloS one

2017 Volume 12, Issue 1, Page(s) e0170539

Abstract: This corrects the article DOI: 10.1371/journal.pone.0158888.]. ...

Abstract	[This corrects the article DOI: 10.1371/journal.pone.0158888.].
Language	English
Publishing date	2017-01-13
Publishing country	United States
Document type	Published Erratum
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0170539
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 ; Online: Selective Killing of SMARCA2- and SMARCA4-deficient Small Cell Carcinoma of the Ovary, Hypercalcemic Type Cells by Inhibition of EZH2:

Chan-Penebre, Elayne / Armstrong, Kelli / Drew, Allison / Grassian, Alexandra R / Feldman, Igor / Knutson, Sarah K / Kuplast-Barr, Kristy / Roche, Maria / Campbell, John / Ho, Peter / Copeland, Robert A / Chesworth, Richard / Smith, Jesse J / Keilhack, Heike / Ribich, Scott A

Molecular cancer therapeutics

2017 Volume 16, Issue 5, Page(s) 850–860

Abstract: The SWI/SNF complex is a major regulator of gene expression and is increasingly thought to play an important role in human cancer, as evidenced by the high frequency of subunit mutations across virtually all cancer types. We previously reported that in ... ...

Abstract	The SWI/SNF complex is a major regulator of gene expression and is increasingly thought to play an important role in human cancer, as evidenced by the high frequency of subunit mutations across virtually all cancer types. We previously reported that in preclinical models, malignant rhabdoid tumors, which are deficient in the SWI/SNF core component INI1 (SMARCB1), are selectively killed by inhibitors of the H3K27 histone methyltransferase EZH2. Given the demonstrated antagonistic activities of the SWI/SNF complex and the EZH2-containing PRC2 complex, we investigated whether additional cancers with SWI/SNF mutations are sensitive to selective EZH2 inhibition. It has been recently reported that ovarian cancers with dual loss of the redundant SWI/SNF components SMARCA4 and SMARCA2 are characteristic of a rare rhabdoid-like subtype known as small-cell carcinoma of the ovary hypercalcemic type (SCCOHT). Here, we provide evidence that a subset of commonly used ovarian carcinoma cell lines were misdiagnosed and instead were derived from a SCCOHT tumor. We also demonstrate that tazemetostat, a potent and selective EZH2 inhibitor currently in phase II clinical trials, induces potent antiproliferative and antitumor effects in SCCOHT cell lines and xenografts deficient in both SMARCA2 and SMARCA4. These results exemplify an additional class of rhabdoid-like tumors that are dependent on EZH2 activity for survival.
MeSH term(s)	Animals ; Carcinoma, Small Cell/diagnosis ; Carcinoma, Small Cell/drug therapy ; Carcinoma, Small Cell/genetics ; Carcinoma, Small Cell/pathology ; Cell Line, Tumor ; Chromosomal Proteins, Non-Histone/genetics ; DNA Helicases/genetics ; Diagnosis, Differential ; Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors ; Enhancer of Zeste Homolog 2 Protein/genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Histone-Lysine N-Methyltransferase/genetics ; Humans ; Hypercalcemia/diagnosis ; Hypercalcemia/drug therapy ; Hypercalcemia/genetics ; Hypercalcemia/pathology ; Mice ; Mutation ; Nuclear Proteins/genetics ; Ovarian Neoplasms/diagnosis ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Rhabdoid Tumor/diagnosis ; Rhabdoid Tumor/drug therapy ; Rhabdoid Tumor/genetics ; Rhabdoid Tumor/pathology ; Transcription Factors/genetics ; Xenograft Model Antitumor Assays
Chemical Substances	Chromosomal Proteins, Non-Histone ; Nuclear Proteins ; SMARCA2 protein, human ; SWI-SNF-B chromatin-remodeling complex ; Transcription Factors ; EZH2 protein, human (EC 2.1.1.43) ; Enhancer of Zeste Homolog 2 Protein (EC 2.1.1.43) ; Histone-Lysine N-Methyltransferase (EC 2.1.1.43) ; SMARCA4 protein, human (EC 3.6.1.-) ; DNA Helicases (EC 3.6.4.-)
Language	English
Publishing date	2017-03-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2063563-1
ISSN	1538-8514 ; 1535-7163
ISSN (online)	1538-8514
ISSN	1535-7163
DOI	10.1158/1535-7163.MCT-16-0678
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5750: 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 ▾
- See ZB MED holdings
- Order with fees

Article: Apoptotic pathways in tumor progression and therapy.

Melet, Armelle / Song, Keli / Bucur, Octavian / Jagani, Zainab / Grassian, Alexandra R / Khosravi-Far, Roya

Advances in experimental medicine and biology

2008 Volume 615, Page(s) 47–79

Abstract: Apoptosis is a cell suicide program that plays a critical role in development and tissue homeostasis. The ability of cancer cells to evade this programmed cell death (PCD) is a major characteristic that enables their uncontrolled growth. The efficiency ... ...

Abstract	Apoptosis is a cell suicide program that plays a critical role in development and tissue homeostasis. The ability of cancer cells to evade this programmed cell death (PCD) is a major characteristic that enables their uncontrolled growth. The efficiency of chemotherapy in killing such cells depends on the successful induction of apoptosis, since defects in apoptosis signaling are a major cause of drug resistance. Over the past decades, much progress has been made in our understanding of apoptotic signaling pathways and their dysregulation in cancer progression and therapy. These advances have provided new molecular targets for proapoptotic cancer therapies that have recently been used in drug development. While most of those therapies are still at the preclinical stage, some of them have shown much promise in the clinic. Here, we review our current knowledge of apoptosis regulation in cancer progression and therapy, as well as the new molecular targeted molecules that are being developed to reinstate cancer cell death.
MeSH term(s)	Animals ; Antineoplastic Agents/therapeutic use ; Apoptosis/physiology ; Disease Progression ; Humans ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Neoplasms/pathology ; Signal Transduction/drug effects
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2008
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-1-4020-6554-5_4
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Preclinical Evidence of Anti-Tumor Activity Induced by EZH2 Inhibition in Human Models of Synovial Sarcoma.

Kawano, Satoshi / Grassian, Alexandra R / Tsuda, Masumi / Knutson, Sarah K / Warholic, Natalie M / Kuznetsov, Galina / Xu, Shanqin / Xiao, Yonghong / Pollock, Roy M / Smith, Jesse S / Kuntz, Kevin K / Ribich, Scott / Minoshima, Yukinori / Matsui, Junji / Copeland, Robert A / Tanaka, Shinya / Keilhack, Heike

PloS one

2016 Volume 11, Issue 7, Page(s) e0158888

Abstract: The catalytic activities of covalent and ATP-dependent chromatin remodeling are central to regulating the conformational state of chromatin and the resultant transcriptional output. The enzymes that catalyze these activities are often contained within ... ...

Abstract	The catalytic activities of covalent and ATP-dependent chromatin remodeling are central to regulating the conformational state of chromatin and the resultant transcriptional output. The enzymes that catalyze these activities are often contained within multiprotein complexes in nature. Two such multiprotein complexes, the polycomb repressive complex 2 (PRC2) methyltransferase and the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeler have been reported to act in opposition to each other during development and homeostasis. An imbalance in their activities induced by mutations/deletions in complex members (e.g. SMARCB1) has been suggested to be a pathogenic mechanism in certain human cancers. Here we show that preclinical models of synovial sarcoma-a cancer characterized by functional SMARCB1 loss via its displacement from the SWI/SNF complex through the pathognomonic SS18-SSX fusion protein-display sensitivity to pharmacologic inhibition of EZH2, the catalytic subunit of PRC2. Treatment with tazemetostat, a clinical-stage, selective and orally bioavailable small-molecule inhibitor of EZH2 enzymatic activity reverses a subset of synovial sarcoma gene expression and results in concentration-dependent cell growth inhibition and cell death specifically in SS18-SSX fusion-positive cells in vitro. Treatment of mice bearing either a cell line or two patient-derived xenograft models of synovial sarcoma leads to dose-dependent tumor growth inhibition with correlative inhibition of trimethylation levels of the EZH2-specific substrate, lysine 27 on histone H3. These data demonstrate a dependency of SS18-SSX-positive, SMARCB1-deficient synovial sarcomas on EZH2 enzymatic activity and suggests the potential utility of EZH2-targeted drugs in these genetically defined cancers.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors ; Enhancer of Zeste Homolog 2 Protein/genetics ; Enhancer of Zeste Homolog 2 Protein/metabolism ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Oncogene Proteins, Fusion/genetics ; Oncogene Proteins, Fusion/metabolism ; Polycomb Repressive Complex 2/genetics ; Polycomb Repressive Complex 2/metabolism ; SMARCB1 Protein/genetics ; SMARCB1 Protein/metabolism ; Sarcoma, Synovial/drug therapy ; Sarcoma, Synovial/genetics ; Sarcoma, Synovial/metabolism ; Xenograft Model Antitumor Assays
Chemical Substances	Antineoplastic Agents ; Oncogene Proteins, Fusion ; SMARCB1 Protein ; SMARCB1 protein, human ; SS18-SSX1 fusion protein ; EZH2 protein, human (EC 2.1.1.43) ; Enhancer of Zeste Homolog 2 Protein (EC 2.1.1.43) ; Polycomb Repressive Complex 2 (EC 2.1.1.43)
Language	English
Publishing date	2016
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0158888
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Full text

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.

Details ▾
- Full text online
- Order with fees

Article ; Online: Isocitrate dehydrogenase (IDH) mutations promote a reversible ZEB1/microRNA (miR)-200-dependent epithelial-mesenchymal transition (EMT).

Grassian, Alexandra R / Lin, Fallon / Barrett, Rosemary / Liu, Yue / Jiang, Wei / Korpal, Manav / Astley, Holly / Gitterman, Daniel / Henley, Thomas / Howes, Rob / Levell, Julian / Korn, Joshua M / Pagliarini, Raymond

The Journal of biological chemistry

2012 Volume 287, Issue 50, Page(s) 42180–42194

Abstract: Mutations in the genes encoding isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in a variety of tumor types, resulting in production of the proposed oncometabolite, 2-hydroxyglutarate (2-HG). How mutant IDH and 2-HG alter signaling pathways to promote ... ...

Abstract	Mutations in the genes encoding isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in a variety of tumor types, resulting in production of the proposed oncometabolite, 2-hydroxyglutarate (2-HG). How mutant IDH and 2-HG alter signaling pathways to promote cancer, however, remains unclear. Additionally, there exist relatively few cell lines with IDH mutations. To examine the effect of endogenous IDH mutations and 2-HG, we created a panel of isogenic epithelial cell lines with either wild-type IDH1/2 or clinically relevant IDH1/2 mutations. Differences were noted in the ability of IDH mutations to cause robust 2-HG accumulation. IDH1/2 mutants that produce high levels of 2-HG cause an epithelial-mesenchymal transition (EMT)-like phenotype, characterized by changes in EMT-related gene expression and cellular morphology. 2-HG is sufficient to recapitulate aspects of this phenotype in the absence of an IDH mutation. In the cells types examined, mutant IDH-induced EMT is dependent on up-regulation of the transcription factor ZEB1 and down-regulation of the miR-200 family of microRNAs. Furthermore, sustained knockdown of IDH1 in IDH1 R132H mutant cells is sufficient to reverse many characteristics of EMT, demonstrating that continued expression of mutant IDH is required to maintain this phenotype. These results suggest mutant IDH proteins can reversibly deregulate discrete signaling pathways that contribute to tumorigenesis.
MeSH term(s)	Amino Acid Substitution ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Glutarates/metabolism ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Humans ; Isocitrate Dehydrogenase/biosynthesis ; Isocitrate Dehydrogenase/genetics ; MicroRNAs/biosynthesis ; MicroRNAs/genetics ; Mutation, Missense ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; RNA, Neoplasm/biosynthesis ; RNA, Neoplasm/genetics ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Up-Regulation/genetics ; Zinc Finger E-box-Binding Homeobox 1
Chemical Substances	Glutarates ; Homeodomain Proteins ; MIRN200 microRNA, human ; MicroRNAs ; Neoplasm Proteins ; RNA, Neoplasm ; Transcription Factors ; ZEB1 protein, human ; Zinc Finger E-box-Binding Homeobox 1 ; alpha-hydroxyglutarate (2889-31-8) ; IDH2 protein, human (EC 1.1.1.41) ; Isocitrate Dehydrogenase (EC 1.1.1.41) ; IDH1 protein, human (EC 1.1.1.42.)
Language	English
Publishing date	2012-10-04
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.M112.417832
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

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Bonn / Germany

Order via subito

Inter-library loan at ZB MED

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

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito