Fig. 2

KRAS, TP53, and MYC cooperatively drive ARF6-mediated cancer malignancy and immune evasion, accompanied with increased mitochondrial activity. Activation of ARF6 by growth factors or LPA triggers a series of intracellular signaling pathways via its downstream effector, AMAP1, that promote cancer cell invasion and metastasis, immune evasion, acidosis, and oxidative/radio-resistance, respectively, and play critical roles in immune evasion and therapeutic resistance (see text for details). ARF6, KRAS, and MYC are inseparable from each other at the molecular level in promoting cancer malignancy and immune evasion. ARF6, KRAS and MYC mRNAs have the G4 structure and require high eIF4A activity for their translation. Thus, the mRNA G4 structure and eIF4A are promising targets to defeat these three evil musketeers in cancer drug development