Much evidence also links hypoxia and extracellular acidosis in VM promotion since crucial VM promoting pathways are shared by these environmental conditions: (1) EMT, initially, is indeed promoted by both hypoxic and acidic conditions [183]; (2) uPAR is over-expressed under hypoxia but also in the presence of low extracellular pH [145]; (3) mTOR is up-regulated under acidic conditions [184] and, in turn, mediates HIF-1α expression [42]; (4) last but not least, both the hypoxic and acidic tumour microenvironments are important for selecting the CSCs and maintenance of stemness [14]. This evidence concerns the gene PLAUR and neoplasm.