Escaping from hypoxia to enjoy normoxia: insights from the social amoeba Dictyostelium

Emerging data indicate that several conditions of oxygen play a pivotal role during cells development, regeneration, and cancer. The directed migration of single cells or cell clumps from hypoxic areas towards a region of optimal oxygen concentration, named aerotaxis, can be considered an adaptive mechanism, playing a major role in several biological and pathological processes. Frequently, O2 gradients develop in tumors given that they grow beyond their vascular supply, leading to heterogeneous areas of O2 depletion and favoring metastatic migration. The aerotaxis process has only recently begun to be explored in higher eucaryotic organisms, and genetically amenable model organisms suitable to dissect this process remains, nowadays, an unmet need. In this regard, we used the social amoeba Dictyostelium discoideum to assess the dynamics and the molecular players regulating the aerotaxis. By measuring different physical parameters, we characterized the phenomenon in both single and aggregating Dictyostelium cells. To identify potential aerotaxis regulators different Dictyostelium mutants were assayed. The outcome reveals that a) on the contrary to chemotaxis, aerotaxis is a G protein-independent process, and b) likewise mammals, an intracellular accumulation of hydrogen peroxide favors the migration toward optimal oxygen concentration. By means of a functional genome wide approach, forecasting the usage of a version of transposon mediated mutagenesis (REMI-seq) we are now attempting to identify the novel molecular players involved in controlling the aerotaxis process.