As mentioned above, malignant transformation and cancer progression depend on reverse pH gradient, and cancer cells maintain higher cytosolic pH (pHc) than non-transformed cells.3 Consistent with the role for STAT3 in the maintenance of alkaline pHc of cancer cells, the pHc of both STAT3-KO clones was significantly lower (7.09 and 7.14) than the pHc of 7.54 in control HeLa cells (Fig. 7a). The gene discussed is STAT3; the disease is cancer.