Pediatrics & Therapeutics
Open Access

Abstract

Cancer and the Cellular Response to Hypoxia

Maria Adamaki, Anastasia Georgountzou and Maria Moschovi

Hypoxia is defined as the reduction of oxygen levels below normal (normoxia), i.e. below 5% and may occur naturally in certain physiological processes such as normal embryo development, stem cell function and angiogenesis. However, hypoxia also plays a major role in many human pathological conditions, including cancer, inflammation, vascular disease and chronic kidney disease. When an organism or tissue is exposed to hypoxia, a series of events takes place within that organism or tissue so as to reinstate oxygen homeostasis. Even though the physiological responses to hypoxia are well-documented, the molecular changes taking place at the cellular level are still being investigated to this very day. Detection of hypoxia by the cell is achieved through oxygen sensor relays residing inside the cell, a class of deoxygenases called PHDs (prolylhydroxylases), which activate special transcription regulators that lead to changes in the gene expression profile of the cell. The changes in gene expression are mainly commanded by a family of hypoxia-responsive transcription factors called HIFs (hypoxia-inducible factors) which, since their discovery in the early 1990s have greatly facilitated molecular research in the field; research on HIFs has led to the discovery of other hypoxia-responsive transcription factors, as well as additional molecular processes that take place following hypoxia, which play a very distinctive role in the transcriptional outcome of the cell. Overall, hypoxia causes a cell cycle arrest at the G1 phase and ultimately, a hypoxia-responsive mechanism for the remodelling of chromatin leads to the activation or repression of specific downstream target genes, to changes in the translational profile of the cell and even to epigenetic post-translational modifications in the cell.