Considering the hypothesis that evolution of glycolytic and acid-resistant phenotypes are key events in progression from in situ to invasive cancer [4], we suppose that hypoxia-induced CAIX which facilitates survival of cancer cells in harsh hypoxia-acidosis-related TME can contribute to the selection of the Warburg effect phenotype through the regulation of LIN28/let-7 axis which target PDK1 expression and enhances glycolytic metabolism. Here, PDK1 is linked to cancer.