The interplay between MYC and HIF in the Warburg effect.

摘要: c-MYC and the hypoxia-inducible factors (HIFs) are critical for tumorigenesis in a large number of human cancers. While normal function MYC involves induction cell proliferation enhancement cellular metabolism, HIF, particularly HIF-1, adaptation to hypoxic microenvironment, including activation anaerobic glycolysis. When MYC-dependent tumors grow, tumor microenvironment elevates levels such that oncogenic HIF collaborate enhance cancer cell's metabolic needs through increased uptake glucose its conversion lactate. is also able attenuate mitochondrial respiration pyruvate dehydrogenase kinase 1 (PDK1), which part accounts Warburg effect describes propensity cancers avidly take up convert it lactate with concurrent decrease respiration. Target genes common both MYC, as PDK1, LDHA, HK2, TFRC, therefore attractive therapeutic targets, because their coordinate by widens window between tissues.