Hypoxia-inducible factor (HIF) is a transcription factor with major roles in many cellular and systemic responses to hypoxia. Activation of HIF pathways under hypoxia is mediated by suppression of the Feand O2-dependent HIF hydroxylase enzymes that normally inactivate HIFA subunits. Mechanisms underlying induction of HIF in normoxic conditions are less clearly understood. In human cancers, infi...

Purpose: To investigate the role of hypoxia-inducible factor-1a (HIF-1a) in angiogenesis and drug resistance of bone marrow endothelial cells of patients with multiple myeloma. Experimental Design: HIF-1a mRNA and protein were evaluated in patients with multiple myeloma endothelial cells (MMEC) at diagnosis, at relapse after bortezomibor lenalidomide-based therapies or on refractory phase to th...

Hypoxia-inducible factor 1 (HIF-1) is a potent tumorigenic factor. Its A subunit (HIF-1A), which is tightly regulated in normal tissues, is elevated in tumors due to hypoxia and overactive growth signaling pathways. Although much is known about HIF-1A regulation in cancer cells, crucial molecular targets that affect HIF-1A levels modulated by both hypoxia and oncogenic signaling pathways remain...

Purpose: Hypoxia-inducible factor 1 (HIF-1) a is frequently overexpressed in human tumors and is associated with angiogenesis and metastasis. Topotecan, a topoisomerase I inhibitor, has been shown to inhibit HIF-1a expression in preclinical models. We designed a pilot trial to measure HIF-1a inhibition in tumor biopsies from patients with advanced solid tumors overexpressing HIF-1a, after treat...

Hypoxia-inducible factor-1A (HIF-1A) seems central to tumor growth and progression because it up-regulates genes essential for angiogenesis and the hypoxic adaptation of cancer cells, which is why HIF-1A inhibition is viewed as a cancer therapy strategy. Paradoxically, HIF-1A also leads to cell cycle arrest or the apoptosis of cancer cells. Thus, the possibility cannot be ruled out that HIF-1A ...

TNF receptor (TNFR)–associated factor TRAF6 is a key activator of NF-kB, playing a critical role in the regulation of innate immune responses and their connection to adaptive immune responses. TRAF6 interactions determine receptor-induced cell death versus survival. TRAF6 has been implicated in cancer but its contributions have not been investigated deeply. In this study, we show that TRAF6 upr...

TNF receptor (TNFR)–associated factor TRAF6 is a key activator of NF-kB, playing a critical role in the regulation of innate immune responses and their connection to adaptive immune responses. TRAF6 interactions determine receptor-induced cell death versus survival. TRAF6 has been implicated in cancer but its contributions have not been investigated deeply. In this study, we show that TRAF6 upr...

Purpose: Hypoxia-inducible factor 1 (HIF-1) a is frequently overexpressed in human tumors and is associated with angiogenesis and metastasis. Topotecan, a topoisomerase I inhibitor, has been shown to inhibit HIF-1a expression in preclinical models. We designed a pilot trial to measure HIF-1a inhibition in tumor biopsies from patients with advanced solid tumors overexpressing HIF-1a, after treat...

Most solid tumors and their metastases experience periods of low oxygen or hypoxia, which is of major clinical significance as it promotes both tumor progression and resistance to therapy. Critical mediators of the hypoxic response are the hypoxia-inducible factors HIF-1a and HIF-2a. The HIFs are nonredundant and regulate both overlapping and unique downstream target genes. Here, we describe a ...

When oxygen supply is restricted, protein synthesis is rapidly abrogated owing to inhibition of global translation. However, HIF-1a protein expression can persist during hypoxia, owing to an internal ribosome entry site (IRES) in the 50-untranslated region of its mRNA. Here, we report on the molecular mechanism of HIF-1a IRES-mediated translation during oxygen deprivation. Using RNA affinity ch...