Fig. 3.

AMPK signaling is inhibited by hyperactive Ras/RAF/MEK/ERK (MAPK) signaling in cancers. a In BRAF(V600E)-harboring cancers, hyperactive ERKs and downstream RSKs phosphorylate LKB1 on Ser325 and Ser428 sites, which inactivates LKB1 and thus blocks the activation of AMPK by LKB1. b In Ras-mutated cancers, the activity of AMPK is partially inhibited likely by hyperactive MAPK signaling, though the underlying molecular mechanism remains ambiguous. However, this moderate AMPK activity is indispensable for disease progression in Ras-mutated cancers