Fig. 8

CCA cells consume glucose more avidly and convert it to lactate, resulting in a low pyruvate level, and this is important for cell proliferation. cMyc decreases pyruvate levels by promoting PKM2 and LDHA levels, consequently decreasing the inhibition to HDAC3 and protecting cancer cells from apoptosis. Conversely, high activity of HDAC3 stabilize the cMyc protein by preferential deacetylation of cMyc at the K323 site, which further contributes to low pyruvate levels. This creates a positive feedback loop that promotes the Warburg effect and cell proliferation of CCA