Cancer cells divert glucose and glutamine into anabolic pathways to support their energy demand for rapid proliferation and accumulation of cellular building blocks required for tumor growth. Here we probed the energetic requirement of metastatic invasion using gene expression profiling and biological validation combined with metabolomic analysis. Migratory cancer cells exhibit a unique glucose metabolism signature that functionally and dynamically support their invasive properties. Interestingly, modulating
such metabolic signature did not impact primary tumor kinetics, however it profoundly altered their potential for dissemination. Our experiments identified specific gene targets that informed us about the bioenergetic switch that fuels invasion and metastasis.