In particular, HIF-1 can regulate the expression and activation of various pH-regulating proteins, such as sodium bicarbonate transporters, sodium-proton exchangers, monocarboxylate transporter-4 (MCT-4), and the carbonic anhydrase IX/XII (CA IX/XII) isoforms, that lead to an inverted pH gradient, typical of cancer cells9, i.e. acidic extracellular pH and slightly more alkaline cytosolic pH values compared to normal ones. This evidence concerns the gene CA9 and cancer.