Numerous studies have shown that supraphysiological activation of AMPK could inhibit
tumor growth. On the other hand, accumulating data also suggest that AMPK activity is required for
tumor growth and migration. These findings suggest that physiological activation of AMPK is critical for
tumor growth/migration, possibly through maintenance of
ATP levels. Our recent study provides the first evidence that the maintenance of cellular
NADPH homeostasis is the predominant mechanism by which AMPK promotes
tumor cell survival and solid
tumor formation. We showed that AMPK activation is required to maintain intracellular
NADPH levels through the activation of
fatty acid oxidation (FAO) or the inhibition of
fatty acid synthesis (FAS) during
glucose deprivation or matrix detachment respectively. Through these processes AMPK activation inhibits the rise in
reactive oxygen species (ROS) levels and promotes metabolic adaptation in response to metabolic stress. This finding also provides a new therapeutic opportunity through targeting metabolic adaptation of
cancer cells, either alone or in combination with conventional anti-
cancer drugs that cause metabolic stress.