I have come across this gene/protein recently and found it as jack of all trade, but i am new to this please add up its role in cancer progression and its immunological correlation if any.
This is an old but much appreciated review on HIF. To begin with, it is a good one.
http://www.nature.com/nrc/journal/v3/n10/full/nrc1187.html
Under hypoxic conditions, which is usually prevalent in the cancer cells (usually in the centre of the tumor mass), HIF induces the expression of VEGF and many other pro-angiogenic factors, by binding to hypoxia response elements in the promoter region of these genes, which promotes angiogenesis i.e., formation of new blood vessels from pre-existing blood vessels. Tumor angiogenesis helps in supplying fuel i.e., oxygen and nutrition to rapidly proliferating cancer cells leading to emergence of macroscopic tumors which may led to distant metastasis.
Under hypoxic conditions, initiation of epithelial-to-mesenchymal transition (EMT) is possible, HIF-signaling may be induced (HIF-1alpha as a transcription factor and marker for acute hypoxia, HIF-2alpha as a transcription factor and marker for chronic hypoxia). EMT occurs during cancer progression (carcinomas), is responsible for cell invasion and metastasis while cells acquire a mesenchymal-like phenotype, i.e. they start to become elongated and motile.
HIF-signaling is one of the possible pathways.
HIF is hypoxia inducible factor and it definitely regulates cancer growth. There are quite a few reviews you can get in pubmed. In your case you can use HIF inhibitors and look at the gene expression of the genes involved in cancer growth. It is a very unstable protein. Alternatively, try using HIF stabilizing agents or culture your cells in hypoxia chamber or use COCl2/DMOG etc. to know your answers.
It is already well known that HIF is intimately tied to the PHD2. There are several exciting papers in literature showing their cooperation in enhancing tumor response to chemotherapy and innate immune response both in cancer and sepsis, as well as vessel normalization in tumors and the regulation of the basal metabolism. Prof. Mazzone at the VRC-VIB (KUL, Belgium) is a specialist in this field of research. Here some of his nice papers.
http://www.ncbi.nlm.nih.gov/pubmed/18176562
http://www.ncbi.nlm.nih.gov/pubmed/19217150
http://www.ncbi.nlm.nih.gov/pubmed/22786772
http://www.ncbi.nlm.nih.gov/pubmed/22897855
Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix protein that activates transcription of the human erythropoietin gene in hypoxic cells. 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. The gene expression that promotes metabolic changes occur during carcinogenesis, beginning with oncogene-mediated changes, followed by hypoxia-induced factor (HIF)-mediated gene expression, both resulting in the highly glycolytic "Warburg" phenotype and suppression of mitochondrial biogenesis. The third (second oncogene) "wave" of adaptation stimulates glutaminolysis, that serves as an alternative pathway compensating for cellular ATP. In cancer cells, HIF-1alpha induces over-expression and increased activity of several glycolytic protein isoforms that differ from those found in non-malignant cells, including transporters (GLUT1, GLUT3) and enzymes (HKI, HKII, PFK-L, ALD-A, ALD-C, PGK1, ENO-alpha, PYK-M2, LDH-A, PFKFB-3).
Hypoxia is one of the cancer stem cells niche element which ensure the survival of cancer stem cells. This condition also turn normal cell into stemness . Hypoxia can be one of the target to eradicate cancer stem cell. I am attaching a paper, hope it could help you
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