HIF-1 is the Commander of Gateways to Cancer

Abstract

The hypoxia-inducible factor-1 (HIF-1) is primarily involved in the sensing and adapting of cells to changes in the O2 level, which is essential for their viability. An increased activity is recognized in the majority of clinical relevant hypoxic/ischemic episodes and human cancers .HIF-1 is considered a central regulator of the adaptation response of cancer cells to hypoxia that makes it a therapeutic target in solid tumors. In this article, the biochemical pathways that are regulated by HIF-1 and the factors that regulate HIF-1 expression are briefly discussed .as targeting HIF-1, may selectively kill tumor cells that adapt to low O2 concentrations. HIF-1 is the Commander of Gateways to CancerNagy MA* Department of Chemistry, College of Science, Beni-Suef University, Beni-Suef, Egypt

Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K

“…HK is the first glycolytic enzyme that facilitates the irreversible conversion of glucose to glucose-6-phosphate in cells, thereby committing the glucose molecule to the glycolytic cycle. Additionally, HIF-1 has been shown to effectively up-regulate many glycolytic enzymes, leading to enhanced glycolysis activity [50]. The enhanced tumour glycolytic flux triggered by HIF-1a also involves changes in the kinetic patterns of expressed isoforms of key glycolytic enzymes, further improving glycolytic energetic capability [50].…”

“…Additionally, HIF-1 has been shown to effectively up-regulate many glycolytic enzymes, leading to enhanced glycolysis activity [50]. The enhanced tumour glycolytic flux triggered by HIF-1a also involves changes in the kinetic patterns of expressed isoforms of key glycolytic enzymes, further improving glycolytic energetic capability [50]. HIF-1 also induces the transcription of pyruvate dehydrogenase kinase 1 (PDK1), which effectively inhibits pyruvate dehydrogenase activity, thereby blocking the conversion of pyruvate the acetyl CoA.…”

“…HIF-1 also induces the transcription of pyruvate dehydrogenase kinase 1 (PDK1), which effectively inhibits pyruvate dehydrogenase activity, thereby blocking the conversion of pyruvate the acetyl CoA. As a consequence, this results in a decreased flux through TCA cycle [50]. This is another result noted in the Warburg effect, thereby showing the HIF-1 activation results in attenuation of the Warburg hypothesis.…”

The Histone Methyltransferase Inhibitor BIX01294 Inhibits HIF-1α Stability and Angiogenesis

“…Therefore, blocking HIF-1α activity is a critical step for inhibiting tumor angiogenesis and growth (Ke and Costa, 2006; Na, 2011). HIF-1 is a heterodimer consisting of an αsubunit and a β subunit.…”

“…Hypoxia inducible factor-1 (HIF-1) is a crucial transcription factor that regulates the expression of target genes involved in angiogenesis, growth factor signaling, cancer cell invasion, and metastasis ( Bardos and Ashcroft, 2005 , Choi et al, 2014 ). Therefore, blocking HIF-1α activity is a critical step for inhibiting tumor angiogenesis and growth ( Ke and Costa, 2006 ; Na, 2011 ). HIF-1 is a heterodimer consisting of an αsubunit and a β subunit.…”