PKM and cholangiocarcinoma: It has been reported that cholangiocarcinoma and colorectal cancer cells maintain low pyruvate by levels by oncogenic c-myc-enhanced expression of LDHA and PKM2 and by limiting pyruvate entry through epigenetic silencing of SLC5A8. This decrease in intracellular pyruvate activates HDAC1/3-mediated transcriptional upregulation of anti-apoptotic proteins Bcl2 and survivin, and downregulation of pro-apoptotic proteins p53 and Bax [41–43].