Fig. 1

Inseparable relationships and cooperation of KRAS, MYC, and ARF6 in cancer. Mutant KRAS induces MYC gene expression and promotes MYC and ARF6 G4-mRNA translation via increasing eIF4A activity. MYC promotes mitochondrial biogenesis and OXPHOS, whereas ARF6 protects mitochondria from oxidative injury by promoting anterograde trafficking of mitochondria which is linked to the activation of integrin recycling and cell invasion by ARF6. Mitochondria generate ATP by OXPHOS, which may promote eIF4A activity, which in turn promotes translation of MYC and ARF6 mRNAs. TP53 mutations enhance glucose uptake, resulting in increased anaerobic ATP production by glycolysis to facilitate the translation of G4 mRNAs even under hypoxia (i.e., low mitochondrial OXPHOS). Enhanced glucose uptake may also fuel mitochondrial metabolism, including OXPHOS. TP53 mutations enhance ARF6 activation and signaling via activating MVP and stopping expression of miRNAs that target AMAP1 mRNA (see Fig. 2)