Amplification of tumor hypoxic responses by macrophage migration inhibitory factor-dependent hypoxia-inducible factor stabilization.

Amplification of tumor hypoxic responses by macrophage migration inhibitory factor-dependent hypoxia-inducible factor stabilization. Research Abstract Details 

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Amplification of tumor hypoxic responses by macrophage migration inhibitory factor-dependent hypoxia-inducible factor stabilization. Abstract Text:

Millicent Winner,Albert C Koong,Beatriz E Rendon,Wayne Zundel,Robert A Mitchell,

Low oxygen tension-mediated transcription by hypoxia-inducible factors (HIF) has been reported to facilitate tumor progression, therapeutic resistance, and metastatic adaptation. One previously described target of hypoxia-mediated transcription is the cytokine/growth factor macrophage migration inhibitory factor (MIF). In studies designed to better understand hypoxia-stimulated MIF function, we have discovered that not only is MIF induced by hypoxia in pancreatic adenocarcinoma but MIF is also necessary for maximal hypoxia-induced HIF-1alpha expression. Cells lacking MIF are defective in hypoxia- and prolyl hydroxylase inhibitor-induced HIF-1alpha stabilization and subsequent transcription of glycolytic and angiogenic gene products. Moreover, COP9 signalosome subunit 5 (CSN5), a component of the COP9 signalosome previously reported to functionally interact with MIF, has recently been shown to interact with and stabilize HIF-1alpha. Our results indicate that MIF interacts with CSN5 in pancreatic cancer cells and that MIF-depleted cells display marked defects in hypoxia-induced CSN5/HIF-1alpha interactions. This functional interdependence between HIF-1alpha and MIF may represent an important and previously unrecognized pro-tumorigenic axis.

Amplification of tumor hypoxic responses by macrophage migration inhibitory factor-dependent hypoxia-inducible factor stabilization. Publishing Authors By Initials

M Winner,AC Koong,BE Rendon,W Zundel,RA Mitchell,

For similar enzymes and coenzymes: enzymes: hydrolases: peptide hydrolases research abstracts see: enzymes and coenzymes: enzymes: hydrolases: peptide hydrolases research

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Amplification of tumor hypoxic responses by macrophage migration inhibitory factor-dependent hypoxia-inducible factor stabilization. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Cancer research

VOLUME: 67

Page Numbers: 186-93

Journal Abbreviation: Cancer Res.

ISSN: 0008-5472

DAY: 1

MONTH: Jan

YEAR: 2007

Amplification of tumor hypoxic responses by macrophage migration inhibitory factor-dependent hypoxia-inducible factor stabilization. Information

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LANGUAGE: eng

NlmUniqueID: 2984705

Amplification of tumor hypoxic responses by macrophage migration inhibitory factor-dependent hypoxia-inducible factor stabilization. Keywords Mesh Terms:

KEYWORDS: Peptide Hydrolases

MESH TERMS: metabolism

Chemical & Substance for Abstract: Amplification of tumor hypoxic responses by macrophage migration inhibitory factor-dependent hypoxia-inducible factor stabilization. Information

Substance Name: Peptide Hydrolases

Registry Number: EC 3.4.-

Grant and Affiliation Information for Amplification of tumor hypoxic responses by macrophage migration inhibitory factor-dependent hypoxia-inducible factor stabilization.

AFFILIATION: Molecular Targets Program, James Graham Brown Cancer Center and Department of Radiation Oncology, University of Louisville, 580 South Preston Street, Louisville, KY, USA.

Country: United States

AGENCY: United States NCI

GRANT: R01 CA 102301

ACRONYM: CA

MEDLINETA: Cancer Res

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