Tumor cells maintain the intracellular pH in an acidic TME by exporting protons through multiple transporters and exchange.16 CA9 converts CO2 into bicarbonate and protons; bicarbonate buffers the intracellular acidity, whereas protons acidify the TME.36 Our data showed that the dysadherin/CA9 axis promotes CRC survival under acidic stress. This evidence concerns the gene FXYD5 and colorectal carcinoma.