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Article ; Online: A Tumor-admixture Model to Interrogate Immune Cell-dependent Tumorigenesis.

Noe, Jordan T / Ding, Chuanlin / Geller, Anne E / Rendon, Beatriz E / Yan, Jun / Mitchell, Robert A

2023 Volume 13, Issue 5

Abstract: A rigorous determination of effector contributions of tumor-infiltrating immune cells is critical for identifying targetable molecular mechanisms for the development of novel cancer immunotherapies. A tumor/immune cell-admixture model is an advantageous ... ...

Abstract	A rigorous determination of effector contributions of tumor-infiltrating immune cells is critical for identifying targetable molecular mechanisms for the development of novel cancer immunotherapies. A tumor/immune cell-admixture model is an advantageous strategy to study tumor immunology as the fundamental methodology is relatively straightforward, while also being adaptable to scale to address increasingly complex research queries. Ultimately, this method can provide robust experimental information to complement more traditional murine models of tumor immunology. Here, we describe a tumor/macrophage-admixture model using bone marrow-derived macrophages to investigate macrophage-dependent tumorigenesis. Additionally, we provide commentary on potential branch points for optimization with other immune cells, experimental techniques, and cancer types.
Language	English
Publishing date	2023-03-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2833269-6
ISSN	2331-8325 ; 2331-8325
ISSN (online)	2331-8325
ISSN	2331-8325
DOI	10.21769/BioProtoc.4630
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Article: MIF inhibition reverts the gene expression profile of human melanoma cell line-induced MDSCs to normal monocytes

Waigel, Sabine / Rendon, Beatriz E / Lamont, Gwyneth / Richie, Jamaal / Mitchell, Robert A / Yaddanapudi, Kavitha

Genomics Data. 2016 Mar., v. 7

2016

Abstract: Myeloid-derived suppressor cells (MDSCs) are potently immunosuppressive innate immune cells that accumulate in advanced cancer patients and actively inhibit anti-tumor T lymphocyte responses [1]. Increased numbers of circulating MDSCs directly correlate ... ...

Abstract	Myeloid-derived suppressor cells (MDSCs) are potently immunosuppressive innate immune cells that accumulate in advanced cancer patients and actively inhibit anti-tumor T lymphocyte responses [1]. Increased numbers of circulating MDSCs directly correlate with melanoma patient morbidity and reduced anti-tumor immune responses [2,3]. Previous studies have revealed that monocyte-derived macrophage migration inhibitory factor (MIF) is necessary for the immune suppressive function of MDSCs in mouse models of melanoma [4,5]. To investigate whether MIF participates in human melanoma-induced MDSC differentiation and/or suppressive function, we have established an in vitro MDSC induction model using primary, normal human monocytes co-cultured with human melanoma cell lines in the presence or absence of the MIF antagonist—4-IPP [4,6–9]. To identify potential mechanistic effectors, we have performed transcriptome analyses on cultured monocytes and on melanoma-induced MDSCs obtained from either untreated or 4-IPP-treated A375:monocyte co-cultures. Here, we present a detailed protocol, which can facilitate easy reproduction of the microarray results (NCBI GEO accession number GSE73333) published by Yaddanapudi et al. (2015) in Cancer Immunology Research [10].
Keywords	animal models ; coculture ; gene expression ; humans ; immune response ; immunosuppression ; macrophage migration inhibitory factors ; melanoma ; microarray technology ; monocytes ; morbidity ; patients ; reproduction ; suppressor cells
Language	English
Dates of publication	2016-03
Size	p. 240-242.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	2751131-5
ISSN	2213-5960
ISSN	2213-5960
DOI	10.1016/j.gdata.2015.12.025
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Article: MIF inhibition reverts the gene expression profile of human melanoma cell line-induced MDSCs to normal monocytes.

Waigel, Sabine / Rendon, Beatriz E / Lamont, Gwyneth / Richie, Jamaal / Mitchell, Robert A / Yaddanapudi, Kavitha

Genomics data

2016 Volume 7, Page(s) 240–242

Abstract	Myeloid-derived suppressor cells (MDSCs) are potently immunosuppressive innate immune cells that accumulate in advanced cancer patients and actively inhibit anti-tumor T lymphocyte responses [1]. Increased numbers of circulating MDSCs directly correlate with melanoma patient morbidity and reduced anti-tumor immune responses [2], [3]. Previous studies have revealed that monocyte-derived macrophage migration inhibitory factor (MIF) is necessary for the immune suppressive function of MDSCs in mouse models of melanoma [4], [5]. To investigate whether MIF participates in human melanoma-induced MDSC differentiation and/or suppressive function, we have established an in vitro MDSC induction model using primary, normal human monocytes co-cultured with human melanoma cell lines in the presence or absence of the MIF antagonist-4-IPP [4], [6], [7], [8], [9]. To identify potential mechanistic effectors, we have performed transcriptome analyses on cultured monocytes and on melanoma-induced MDSCs obtained from either untreated or 4-IPP-treated A375:monocyte co-cultures. Here, we present a detailed protocol, which can facilitate easy reproduction of the microarray results (NCBI GEO accession number GSE73333) published by Yaddanapudi et al. (2015) in Cancer Immunology Research [10].
Language	English
Publishing date	2016-01-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2751131-5
ISSN	2213-5960
ISSN	2213-5960
DOI	10.1016/j.gdata.2015.12.025
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Article: Targeting Melanoma Hypoxia with the Food-Grade Lactic Acid Bacterium

Garza-Morales, Rodolfo / Rendon, Beatriz E / Malik, Mohammad Tariq / Garza-Cabrales, Jeannete E / Aucouturier, Anne / Bermúdez-Humarán, Luis G / McMasters, Kelly M / McNally, Lacey R / Gomez-Gutierrez, Jorge G

Cancers

2020 Volume 12, Issue 2

Abstract: Melanoma is the most aggressive form of skin cancer. Hypoxia is a feature of the tumor microenvironment that reduces efficacy of immuno- and chemotherapies, resulting in poor clinical outcomes. ...

Abstract	Melanoma is the most aggressive form of skin cancer. Hypoxia is a feature of the tumor microenvironment that reduces efficacy of immuno- and chemotherapies, resulting in poor clinical outcomes.
Language	English
Publishing date	2020-02-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12020438
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Article ; Online: Negative regulation of AMP-activated protein kinase (AMPK) activity by macrophage migration inhibitory factor (MIF) family members in non-small cell lung carcinomas.

Brock, Stephanie E / Rendon, Beatriz E / Yaddanapudi, Kavitha / Mitchell, Robert A

The Journal of biological chemistry

2012 Volume 287, Issue 45, Page(s) 37917–37925

Abstract: AMP-activated protein kinase (AMPK) is a nutrient- and metabolic stress-sensing enzyme activated by the tumor suppressor kinase, LKB1. Because macrophage migration inhibitory factor (MIF) and its functional homolog, d-dopachrome tautomerase (d-DT), have ... ...

Abstract	AMP-activated protein kinase (AMPK) is a nutrient- and metabolic stress-sensing enzyme activated by the tumor suppressor kinase, LKB1. Because macrophage migration inhibitory factor (MIF) and its functional homolog, d-dopachrome tautomerase (d-DT), have protumorigenic functions in non-small cell lung carcinomas (NSCLCs) but have AMPK-activating properties in nonmalignant cell types, we set out to investigate this apparent paradox. Our data now suggest that, in contrast to MIF and d-DTs AMPK-activating properties in nontransformed cells, MIF and d-DT act cooperatively to inhibit steady-state phosphorylation and activation of AMPK in LKB1 wild type and LKB1 mutant human NSCLC cell lines. Our data further indicate that MIF and d-DT, acting through their shared cell surface receptor, CD74, antagonize NSCLC AMPK activation by maintaining glucose uptake, ATP production, and redox balance, resulting in reduced Ca(2+)/calmodulin-dependent kinase kinase β-dependent AMPK activation. Combined, these studies indicate that MIF and d-DT cooperate to inhibit AMPK activation in an LKB1-independent manner.
MeSH term(s)	AMP-Activated Protein Kinases/genetics ; AMP-Activated Protein Kinases/metabolism ; Acetylcysteine/pharmacology ; Antigens, Differentiation, B-Lymphocyte/genetics ; Antigens, Differentiation, B-Lymphocyte/metabolism ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/metabolism ; Carcinoma, Non-Small-Cell Lung/pathology ; Cell Line, Tumor ; Deoxyglucose/pharmacology ; Enzyme Activation/drug effects ; Free Radical Scavengers/pharmacology ; Glucose/pharmacokinetics ; Glucose/pharmacology ; Histocompatibility Antigens Class II/genetics ; Histocompatibility Antigens Class II/metabolism ; Humans ; Immunoblotting ; Intramolecular Oxidoreductases/genetics ; Intramolecular Oxidoreductases/metabolism ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Macrophage Migration-Inhibitory Factors/genetics ; Macrophage Migration-Inhibitory Factors/metabolism ; Mutation ; Oxidation-Reduction/drug effects ; Phosphorylation/drug effects ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; RNA Interference ; Reactive Oxygen Species/antagonists & inhibitors ; Reactive Oxygen Species/metabolism ; Signal Transduction/drug effects ; TOR Serine-Threonine Kinases/metabolism
Chemical Substances	Antigens, Differentiation, B-Lymphocyte ; Free Radical Scavengers ; Histocompatibility Antigens Class II ; Macrophage Migration-Inhibitory Factors ; Reactive Oxygen Species ; invariant chain ; Deoxyglucose (9G2MP84A8W) ; STK11 protein, human (EC 2.7.1.-) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; Intramolecular Oxidoreductases (EC 5.3.-) ; dopachrome isomerase (EC 5.3.3.12) ; Glucose (IY9XDZ35W2) ; Acetylcysteine (WYQ7N0BPYC)
Language	English
Publishing date	2012-09-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M112.378299
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Article ; Online: MIF family members cooperatively inhibit p53 expression and activity.

Brock, Stephanie E / Rendon, Beatriz E / Xin, Dan / Yaddanapudi, Kavitha / Mitchell, Robert A

PloS one

2014 Volume 9, Issue 6, Page(s) e99795

Abstract: The tumor suppressor p53 is induced by genotoxic stress in both normal and transformed cells and serves to transcriptionally coordinate cell cycle checkpoint control and programmed cell death responses. Macrophage migration inhibitory factor (MIF) is an ... ...

Abstract	The tumor suppressor p53 is induced by genotoxic stress in both normal and transformed cells and serves to transcriptionally coordinate cell cycle checkpoint control and programmed cell death responses. Macrophage migration inhibitory factor (MIF) is an autocrine and paracrine acting cytokine/growth factor that promotes lung adenocarcinoma cell motility, anchorage-independence and neo-angiogenic potential. Several recent studies indicate that the only known homolog of MIF, D-dopachrome tautomerase (D-DT - also referred to as MIF-2), has functionally redundant activities with MIF and cooperatively promotes MIF-dependent pro-tumorigenic phenotypes. We now report that MIF and D-DT synergistically inhibit steady state p53 phosphorylation, stabilization and transcriptional activity in human lung adenocarcinoma cell lines. The combined loss of MIF and D-DT by siRNA leads to dramatically reduced cell cycle progression, anchorage independence, focus formation and increased programmed cell death when compared to individual loss of MIF or D-DT. Importantly, p53 mutant and p53 null lung adenocarcinoma cell lines were only nominally rescued from the cell growth effects of MIF/D-DT combined deficiency suggesting only a minor role for p53 in these transformed cell growth phenotypes. Finally, increased p53 activation was found to be independent of aberrantly activated AMP-activated protein kinase (AMPK) that occurs in response to MIF/D-DT-deficiency but is dependent on reactive oxygen species (ROS) that mediate aberrant AMPK activation in these cells. Combined, these findings suggest that both p53 wildtype and mutant human lung adenocarcinoma tumors rely on MIF family members for maximal cell growth and survival.
MeSH term(s)	AMP-Activated Protein Kinases ; Carcinoma, Non-Small-Cell Lung/metabolism ; Carcinoma, Non-Small-Cell Lung/pathology ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Clone Cells ; Humans ; Intramolecular Oxidoreductases/deficiency ; Intramolecular Oxidoreductases/metabolism ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Macrophage Migration-Inhibitory Factors/deficiency ; Macrophage Migration-Inhibitory Factors/metabolism ; Oxidation-Reduction ; Oxidative Stress ; Phenotype ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Macrophage Migration-Inhibitory Factors ; Tumor Suppressor Protein p53 ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; Intramolecular Oxidoreductases (EC 5.3.-) ; dopachrome isomerase (EC 5.3.3.12)
Language	English
Publishing date	2014-06-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0099795
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Article ; Online: Lactate supports a metabolic-epigenetic link in macrophage polarization.

Science advances

2021 Volume 7, Issue 46, Page(s) eabi8602

Abstract: Lactate accumulation is a hallmark of solid cancers and is linked to the immune suppressive phenotypes of tumor-infiltrating immune cells. We report herein that interleukin-4 (IL-4)–induced M0 → M2 macrophage polarization is accompanied by ... ...

Abstract	Lactate accumulation is a hallmark of solid cancers and is linked to the immune suppressive phenotypes of tumor-infiltrating immune cells. We report herein that interleukin-4 (IL-4)–induced M0 → M2 macrophage polarization is accompanied by interchangeable glucose- or lactate-dependent tricarboxylic acid (TCA) cycle metabolism that directly drives histone acetylation, M2 gene transcription, and functional immune suppression. Lactate-dependent M0 → M2 polarization requires both mitochondrial pyruvate uptake and adenosine triphosphate–citrate lyase (ACLY) enzymatic activity. Notably, exogenous acetate rescues defective M2 polarization and histone acetylation following mitochondrial pyruvate carrier 1 (MPC1) inhibition or ACLY deficiency. Lastly, M2 macrophage–dependent tumor progression is impaired by conditional macrophage ACLY deficiency, further supporting a dominant role for glucose/lactate mitochondrial metabolism and histone acetylation in driving immune evasion. This work adds to our understanding of how mitochondrial metabolism affects macrophage functional phenotypes and identifies a unique tumor microenvironment (TME)–driven metabolic-epigenetic link in M2 macrophages.
Language	English
Publishing date	2021-11-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.abi8602
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Article ; Online: Mechanisms of macrophage migration inhibitory factor (MIF)-dependent tumor microenvironmental adaptation.

Rendon, Beatriz E / Willer, Sharon S / Zundel, Wayne / Mitchell, Robert A

Experimental and molecular pathology

2009 Volume 86, Issue 3, Page(s) 180–185

Abstract: Since its activity was first reported in the mid-1960s, macrophage migration inhibitory factor (MIF) has gone from a cytokine activity modulating monocyte motility to a pleiotropic regulator of a vast array of cellular and biological processes. Studies ... ...

Abstract	Since its activity was first reported in the mid-1960s, macrophage migration inhibitory factor (MIF) has gone from a cytokine activity modulating monocyte motility to a pleiotropic regulator of a vast array of cellular and biological processes. Studies in recent years suggest that MIF contributes to malignant disease progression on several different levels. Both circulating and intracellular MIF protein levels are elevated in cancer patients and MIF expression reportedly correlates with stage, metastatic spread and disease-free survival. Additionally, MIF expression positively correlates with angiogenic growth factor expression, microvessel density and tumor-associated neovascularization. Not coincidentally, MIF has recently been shown to contribute to tumoral hypoxic adaptation by promoting hypoxia-induced HIF-1alpha stabilization. Intriguingly, hypoxia is a strong regulator of MIF expression and secretion, suggesting that hypoxia-induced MIF acts as an amplifying factor for both hypoxia and normoxia-associated angiogenic growth factor expression in human malignancies. Combined, these findings suggest that MIF overexpression contributes to tumoral hypoxic adaptation and, by extension, therapeutic responsiveness and disease prognosis. This review summarizes recent literature on the contributions of MIF to tumor-associated angiogenic growth factor expression, neovascularization and hypoxic adaptation. We also will review recent efforts aimed at identifying and employing small-molecule antagonists of MIF as a novel approach to cancer therapeutics.
MeSH term(s)	Adaptation, Physiological ; Animals ; Antineoplastic Agents/pharmacology ; Drug Discovery ; Female ; Humans ; Hypoxia/physiopathology ; Hypoxia-Inducible Factor 1, alpha Subunit/physiology ; Intramolecular Oxidoreductases/antagonists & inhibitors ; Intramolecular Oxidoreductases/chemistry ; Intramolecular Oxidoreductases/physiology ; Macrophage Migration-Inhibitory Factors/antagonists & inhibitors ; Macrophage Migration-Inhibitory Factors/chemistry ; Macrophage Migration-Inhibitory Factors/physiology ; Male ; Molecular Structure ; Neoplasms/blood supply ; Neoplasms/drug therapy ; Neoplasms/physiopathology ; Neovascularization, Pathologic
Chemical Substances	Antineoplastic Agents ; Hypoxia-Inducible Factor 1, alpha Subunit ; Macrophage Migration-Inhibitory Factors ; Intramolecular Oxidoreductases (EC 5.3.-) ; MIF protein, human (EC 5.3.2.1)
Language	English
Publishing date	2009-01-07
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	207655-x
ISSN	1096-0945 ; 0014-4800
ISSN (online)	1096-0945
ISSN	0014-4800
DOI	10.1016/j.yexmp.2009.01.001
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Article ; Online: MIF Is Necessary for Late-Stage Melanoma Patient MDSC Immune Suppression and Differentiation.

Yaddanapudi, Kavitha / Rendon, Beatriz E / Lamont, Gwyneth / Kim, Eun Jung / Al Rayyan, Numan / Richie, Jamaal / Albeituni, Sabrin / Waigel, Sabine / Wise, Ashley / Mitchell, Robert A

Cancer immunology research

2016 Volume 4, Issue 2, Page(s) 101–112

Abstract: Highly aggressive cancers "entrain" innate and adaptive immune cells to suppress antitumor lymphocyte responses. Circulating myeloid-derived suppressor cells (MDSC) constitute the bulk of monocytic immunosuppressive activity in late-stage melanoma ... ...

Abstract	Highly aggressive cancers "entrain" innate and adaptive immune cells to suppress antitumor lymphocyte responses. Circulating myeloid-derived suppressor cells (MDSC) constitute the bulk of monocytic immunosuppressive activity in late-stage melanoma patients. Previous studies revealed that monocyte-derived macrophage migration inhibitory factor (MIF) is necessary for the immunosuppressive function of tumor-associated macrophages and MDSCs in mouse models of melanoma. In the current study, we sought to determine whether MIF contributes to human melanoma MDSC induction and T-cell immunosuppression using melanoma patient-derived MDSCs and an ex vivo coculture model of human melanoma-induced MDSC. We now report that circulating MDSCs isolated from late-stage melanoma patients are reliant upon MIF for suppression of antigen-independent T-cell activation and that MIF is necessary for maximal reactive oxygen species generation in these cells. Moreover, inhibition of MIF results in a functional reversion from immunosuppressive MDSC to an immunostimulatory dendritic cell (DC)-like phenotype that is at least partly due to reductions in MDSC prostaglandin E(2) (PGE(2)). These findings indicate that monocyte-derived MIF is centrally involved in human monocytic MDSC induction/immunosuppressive function and that therapeutic targeting of MIF may provide a novel means of inducing antitumor DC responses in late-stage melanoma patients.
MeSH term(s)	Animals ; Biomarkers ; Cell Differentiation ; Cell Line, Tumor ; Disease Models, Animal ; Humans ; Immunophenotyping ; Macrophage Migration-Inhibitory Factors/metabolism ; Male ; Melanoma/immunology ; Melanoma/metabolism ; Melanoma/pathology ; Mice ; Mice, Transgenic ; Myeloid Cells/immunology ; Myeloid Cells/metabolism ; Myeloid Cells/pathology ; Neoplasm Grading ; Neoplasm Staging ; Phenotype ; Reactive Oxygen Species/metabolism
Chemical Substances	Biomarkers ; Macrophage Migration-Inhibitory Factors ; Reactive Oxygen Species
Language	English
Publishing date	2016-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2732489-8
ISSN	2326-6074 ; 2326-6066
ISSN (online)	2326-6074
ISSN	2326-6066
DOI	10.1158/2326-6066.CIR-15-0070-T
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Article: Rho GTPase-dependent signaling is required for macrophage migration inhibitory factor-mediated expression of cyclin D1.

Swant, James D / Rendon, Beatriz E / Symons, Marc / Mitchell, Robert A

The Journal of biological chemistry

2005 Volume 280, Issue 24, Page(s) 23066–23072

Abstract: Our previous studies demonstrated that the proinflammatory peptide, macrophage migration inhibitory factor (MIF), functions as an autocrine mediator of both growth factor- and integrin-dependent sustained ERK MAPK activation, cyclin D1 expression, and ... ...

Abstract	Our previous studies demonstrated that the proinflammatory peptide, macrophage migration inhibitory factor (MIF), functions as an autocrine mediator of both growth factor- and integrin-dependent sustained ERK MAPK activation, cyclin D1 expression, and cell cycle progression. We now report that MIF promotes the activation of the canonical ERK MAPK cascade and cyclin D1 expression by stimulating the activity of the Rho GTPase and downstream signaling to stress fiber formation. Rho-dependent stress fiber accumulation promotes the sustained activation of ERK and subsequent cyclin D1 expression during G(1)-S phase cell cycle progression. This pathway is reported to be dependent upon myosin light chain (MLC) kinase, integrin clustering, and subsequent activation of focal adhesion kinase, leading to sustained MAPK activity. Our studies reveal that recombinant MIF induces cyclin D1 expression in a Rho-, Rho kinase-, MLC kinase-, and ERK-dependent manner in asynchronous NIH 3T3 fibroblasts. Moreover, MIF(-/-) murine embryonic fibroblasts display aberrant cyclin D1 expression that is linked to defective Rho activity, stress fiber formation, and MLC phosphorylation. These results suggest that MIF is an integral autocrine mediator of Rho GTPase-dependent signaling events and provide mechanistic insight into how MIF regulates proliferative, migratory, and oncogenic processes.
MeSH term(s)	Animals ; Cell Movement ; Cell Proliferation ; Cell Transformation, Neoplastic ; Cyclin D1/biosynthesis ; Cyclin D1/metabolism ; Dose-Response Relationship, Drug ; Enzyme Activation ; Fibroblasts/metabolism ; Glutathione Transferase/metabolism ; Immunoblotting ; Luciferases/metabolism ; MAP Kinase Signaling System ; Macrophage Migration-Inhibitory Factors/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microscopy, Fluorescence ; Models, Biological ; Myosin-Light-Chain Kinase/metabolism ; NIH 3T3 Cells ; Phosphorylation ; Plasmids/metabolism ; Retroviridae/genetics ; Signal Transduction ; Time Factors ; rho GTP-Binding Proteins/metabolism
Chemical Substances	Macrophage Migration-Inhibitory Factors ; Cyclin D1 (136601-57-5) ; Luciferases (EC 1.13.12.-) ; Glutathione Transferase (EC 2.5.1.18) ; Myosin-Light-Chain Kinase (EC 2.7.11.18) ; rho GTP-Binding Proteins (EC 3.6.5.2)
Language	English
Publishing date	2005-04-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M500636200
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