Macropinocytosis is an endocytic process that provides cancer cells with the ability to uptake proteins and extracellular fluids into large intracellular vesicles known as macropinosomes.
Consequently, in the harsh tumor microenvironment where no nutrients and oxygen are available, macropinocytosis can represent a unique source of amino acids to allow survival. By using patientderived glioblastoma stem cells, we identified and characterized a subset of Gal-3high GBM tumors mainly within the mesenchymal subtype that are addicted to Gal-3/RAB10/β1 integrin complex-mediated macropinocytosis. In our study, we revealed a significant decrease of GSC macropinocytosis activity, cell survival and invasion, in vitro and in vivo was achieved using both genetic and pharmacologic inhibition of Gal-3.