Targeting Angiogenesis via a c-Myc/Hypoxia-Inducible Factor-1α–Dependent Pathway in Multiple Myeloma

2009 ◽  
Vol 69 (12) ◽  
pp. 5082-5090 ◽  
Author(s):  
Jing Zhang ◽  
Martin Sattler ◽  
Giovanni Tonon ◽  
Clemens Grabher ◽  
Samir Lababidi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1Α ◽  
Dependent Pathway

scholarly journals Cobalt Chloride-Induced Estrogen Receptor α Down-Regulation Involves Hypoxia-Inducible Factor-1α in MCF-7 Human Breast Cancer Cells

2005 ◽  
Vol 19 (5) ◽  
pp. 1191-1199 ◽  
Author(s):  
Jungyoon Cho ◽  
Dukkyung Kim ◽  
SeungKi Lee ◽  
YoungJoo Lee
Keyword(s):  
Estrogen Receptor ◽  
Protein Interactions ◽  
Cobalt Chloride ◽  
Active Form ◽  
Hypoxia Inducible Factor ◽  
Dependent Manner ◽  
Transactivation Domain ◽  
Down Regulation ◽  
Hypoxia Inducible Factor 1Α ◽  
Dependent Pathway

Abstract The estrogen receptor (ER) is down-regulated under hypoxia via a proteasome-dependent pathway. We studied the mechanism of ERα degradation under hypoxic mimetic conditions. Cobalt chloride-induced ERα down-regulation was dependent on the expression of newly synthesized protein(s), one possibility of which was hypoxia-inducible factor-1α (HIF-1α). To examine the role of HIF-1α expression in ERα down-regulation under hypoxic-mimetic conditions, we used a constitutively active form of HIF-1α, HIF-1α/herpes simplex viral protein 16 (VP16), constructed by replacing the transactivation domain of HIF-1α with that of VP16. Western blot analysis revealed that HIF-1α/VP16 down-regulated ERα in a dose-dependent manner via a proteasome-dependent pathway. The kinase pathway inhibitors PD98059, U0126, wortmannin, and SB203580 did not affect the down-regulation. A mammalian two-hybrid screen and immunoprecipitation assays indicated that ERα interacted with HIF-1α physically. These results suggest that ERα down-regulation under hypoxia involves protein-protein interactions between the ERα and HIF-1α.

scholarly journals Hypoxia-induced IL-18 Increases Hypoxia-inducible Factor-1α Expression through a Rac1-dependent NF-κB Pathway

2008 ◽  
Vol 19 (2) ◽  
pp. 433-444 ◽  
Author(s):  
Jeongki Kim ◽  
Yan Shao ◽  
Sang Yong Kim ◽  
Seyl Kim ◽  
Hyun Keun Song ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tumor Cell ◽  
Tumor Progression ◽  
Hypoxia Inducible Factor ◽  
Inflammatory Cells ◽  
Interleukin 18 ◽  
Hypoxia Inducible Factor 1Α ◽  
Cell Metastasis ◽  
Tumor Cell Metastasis ◽  
Dependent Pathway

Interleukin-18 (IL-18) plays pivotal roles in linking inflammatory immune responses and tumor progression and metastasis, yet the manner in which this occurs remains to be sufficiently clarified. Here we report that hypoxia induces the transcription and secretion of IL-18, which subsequently induces the expression of hypoxia-inducible factor-1α (HIF-1α). Mechanistically, IL-18 induces HIF-1α through the activity of the GTPase Rac1, which inducibly associates with the IL-18 receptor β (IL-18Rβ) subunit, via a PI3K-AKT-NF-κB–dependent pathway. Importantly, the knockdown of the IL-18Rβ subunit inhibited IL-18–driven tumor cell metastasis. Collectively, these findings demonstrate a feed-forward pathway in HIF-1α–mediated tumor progression, in which the induction of IL-18 by hypoxia or inflammatory cells augments the expression of both HIF-1α and tumor cell metastasis.

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