Up-down regulation of HIF-1α in cancer progression

Hypoxia induicible factor-1 alpha (HIF-1 alpha) is a key transcription factor in cancer progression and target therapy in cancer. HIF-1 alpha acts differently depending on presence or absence of Oxygen. In an oxygen-immersed environment, HIF-1 alpha completely deactivated and destroyed by the ubiquitin proteasome pathway (UPP). In contrast, in the oxygen-free environment, it escapes destruction and enters to the nucleus of cells then upregulates many genes involved in cancer progression. Overexpressed HIF-1 alpha and downstream genes support cancer progression through various mechanisms including angiogenesis, proliferation and survival of cells, metabolism reprogramming, invasion and metastasis, cancer stem cell maintenance, induction of genetic instability, and treatment resistance. HIF-1 alpha can be provoked by signaling pathways unrelated to hypoxia during cancer progression. Therefore, cancer development and progression can be modulated by targeting HIF-1 alpha and its downstream signaling molecules. In this regard, HIF-1 alpha inhibitors which are categorized into the agents that regulate HIF-1 alpha in gene, mRNA and protein levels used as an efficient way in cancer treatment. Also, HIF-1 alpha expression can be negatively affected by the agents suppressing the activation of mTOR, PI3k/Akt and MAPK pathways.