Title:Role of HIF-1 in Cancer Progression: Novel Insights. A Review
VOLUME: 18 ISSUE: 6
Author(s):Aldo Pezzuto* and Elisabetta Carico
Affiliation:Department of Cardiovascular and Pulmonary Science S. Andrea Hospital -Sapienza University, Rome, Department of Clinical and Molecular Medicine, S. Andrea Hospital -Sapienza University, Rome
Keywords:HIF-1, metastases, tumor progression, hypoxia, microenvironment, metabolic pathways.
Abstract:Hypoxia is a condition always present in tumor environment owing to the fast
growth of tumor cells not supported by adequate blood supply.
There is increasing evidence that hypoxia plays an important role in cancer dormancy
and cancer metabolism, increasing stemness activity and bringing about cancer initiation
and progression.
This condition may influence the production of hypoxia inducible factor (HIF) a helix
transcription factor which is involved in carcinogenesis and tumor growth through the
regulation of genes involved in angiogenesis, glycolytic metabolism and other biological
mechanisms.
In normoxia condition HIF is inactivated by prolyl hydroxylase enzymes (EGLN 1–3, also
known as PHD 1–3) using oxygen as a substrate. Once hydroxilated it binds to a protein
called Von Hippel Lindau protein (VHL) for its degradation, whereas in hypoxia condition
stabilization and nuclear translocation occur, leading to oncogenes activation. It has got
three isoforms HIF-1 HIF-2 and HIF-3. The most studied factor is HIF-1 which is a
heterodimer consisting of two forms, the form α is expressed in manner oxygen
dependent, the form β is expressed constitutively.
Its presence in tumor microenvironment could foster among other the expression of
VEGF, HGF, Met protoncogene which induces degradation of the extracellular matrix
and TWIST gene, which is in turn involved in a mechanism of cancer cell metastasis
called epithelial-mesenchimal transition(EMT). In this review, we summarize the most
important findings in HIF action in different types of cancer focusing on its properties to
induce tumor cell growth and highlighting its poor prognostic value in different cancers
sites.
