HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability.

By J. Isaacs, Yun-jin Jung, D. Mole, Sunmin Lee, C. Torres‐Cabala, Yuen-Li Chung, Maria J Merino, J. Trepel, B. Zbar, J. Toro and 3 more. Cancer Cell, 2005

965 citations recorded by the source corpus.

Subfields: Cancer Research, Pulmonary and Respiratory Medicine, Surgery

View Paper: https://www.semanticscholar.org/paper/6906ef0c1fe45571640c3c7a6b3c9c2d9a979a64

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

In Pulmonary and Respiratory Medicine

In Surgery

Citations in the corpus

Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate (2012, background): “Several independent groups have failed to observe a direct link between 2HG and PHD2 inhibition.”
Cancer cell metabolism: Warburg and beyond. (2008, background): “…has been proposed that loss of succinate dehydrogenase and fumarate hydratase causes an accumulation of succinate or fumarate, respectively, leading to inhibition of the prolyl hydroxylases that mark HIF for VHL-mediated degradation (Isaacs et al., 2005; Pollard et al., 2005; Selak et al., 2005).”
Role of Mitochondria in Ferroptosis (2018, background): “FH defect leads to aberrant accumulation of fumarate, which in turn inactivates prolyl hydroxylases and thus stabilizes hypoxia-inducible factor (HIF)-1α (Isaacs et al., 2005; Selak et al., 2005).”
The oncometabolite 2‐hydroxyglutarate inhibits histone lysine demethylases (2011, background): “The HIF hydroxylases function as negative regulators of HIF-mediated transcription”
ADAPTIVE AND MALADAPTIVE CARDIORESPIRATORY RESPONSES TO CONTINUOUS AND INTERMITTENT HYPOXIA MEDIATED BY HYPOXIA-INDUCIBLE FACTORS 1 AND 2 (2012, background): “Metabolite induction of HIF-1 results from inhibition of PHD2 activity (114, 131, 162, 201, 296).”
Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. (2008, background): “Krebs Cycle and Other Metabolic Intermediates In addition to requiring 2-oxoglutarate as a cosubstrate, the HIF hydroxylases have been reported to be inhibited by citrate, isocitrate, succinate, fumarate, malate, oxaloacetate, and pyruvate (Dalgard et al., 2004; Hewitson et al., 2007; Isaacs et al.,”
Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer (2006, background): “Although both molecules were shown to mediate HIF induction (Isaacs et al., 2005; Selak et al., 2005), it is possible that they inhibit different PHDs with different efficiency.”
Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of α-Ketoglutarate-Dependent Dioxygenases (2011, background): “Mutations targeting FH and SDH lead to similar increase in the PHD substrate, HIF-1a (Isaacs et al., 2005; Pollard et al., 2005; Selak et al., 2005).”
Advances in Hypoxia-Inducible Factor Biology. (2017, background): “Accumulation of fumarate and succinate metabolites can increase HIF-1α levels and expression of HIF target genes in part by inhibiting the PHD enzymes in cancer cells (Isaacs et al., 2005; Selak et al., 2005).”
Repurposing mitochondria from ATP production to ROS generation drives a pro-inflammatory phenotype in macrophages that depends on succinate oxidation by complex II (2016, background): “However, it is known that fumarate can stabilize HIF-1a, and this is likely the mechanism by which it is inducing IL-1b (Isaacs et al., 2005).”