DAYAN , Frédéric

Tumour cells emerge as a result of genetic alteration of signal circuitries promoting cell growth and survival, whereas their expansion relies on nutrient supply. Oxygen limitation is central in controlling neovascularization, glucose metabolism, survival and tumour spread. This pleiotropic action is orchestrated by hypoxia-inducible factor...

Hif, being the master protein involved in adaptation to low p[O], plays a major role in many physiological and pathological phenomena: development, inflammation, ischemia and cancer. PHD and FIH are the two oxygen sensors that regulate the Hif pathway. Here we model the regulatory dynamics in an oxygen gradient by a system of differential...

The hypoxia-inducible factor is the key protein responsible for the cellular adaptation to low oxygen tension. This transcription factor becomes activated as a result of a drop in the partial pressure of oxygen, to hypoxic levels below 5% oxygen, and targets a panel of genes involved in maintenance of oxygen homeostasis. Hypoxia is a common...

The function of the hypoxia-inducible factor-1 (HIF-1), the key transcription factor involved in cellular adaptation to hypoxia, is restricted to low oxygen tension (pO(2)). As such, this transcription factor is central in modulating the tumor microenvironment, sensing nutrient availability, and controlling anaerobic glycolysis, intracellular...

International audience

This chapter describes basic principles for modeling genetic regulatory networks, using three different classes of formalisms: discrete, hybrid, and continuous differential systems. A short review of the mathematical tools for each formalism is presented. Based on several simple examples, which are worked out in detail, this chapter illustrates...

Accumulation of HIF-1alpha during normoxic conditions at high cell density has previously been shown to occur and can be used to stabilize HIF-1alpha protein in the absence of a specific anaerobic chamber. However, the impact and origin of this pool of HIF-1alpha, obtained under normoxia, has been underestimated. In this study, we have...

Acidosis of the tumor microenvironment is typical of a malignant phenotype, particularly in hypoxic tumors. All cells express multiple isoforms of carbonic anhydrase (CA), enzymes catalyzing the reversible hydration of carbon dioxide into bicarbonate and protons. Tumor cells express membrane-bound CAIX and CAXII that are controlled via the...

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. It is important that this critical transcription factor be tightly regulated in order for cells to respond to a wide range of O2 concentrations. HIF-1 regulation by...

Adaptation to hypoxia is a driving force for tumor progression that leads to therapy resistance and poor clinical outcome. Hypoxic responses are mainly mediated by hypoxia-inducible factor-1 (HIF-1). One critical HIF-1 target mediating tumor progression is lysyl oxidase (LOX), which catalyzes cross-linking of collagens and elastin in the...