Activation of AMPK promotes thyroid cancer cell migration through its interaction with PKM2 and beta-catenin

摘要

AMP-activated protein kinase (AMPK) is induced by the exhaustion of cellular energy and activates adaptive alterations in cellular metabolism, which is the basis for cell survival during different environmental stresses. We aimed to investigate the biological functions of AMPK and its molecular mechanism in regulating thyroid cancer (TC) progression. In current study, we found that activation of AMPK by multiple agonists suppresses TC cell proliferation. However, AMPK activation also led to TC cell migration at the same time. Depletion of AMPK abolished the effect of its agonist on cell multiplication and migration. Mechanistic investigations revealed that the impact of AMPK in terms of cell migration is dependent on its nuclear translocation, since site mutation of AMPK in its nuclear translocation domain (K244A) abolished TC cell migration but did not affect the inhibition of cell proliferation by AMPK agonist. Moreover, the nuclear AMPK recruits PKM2 and beta-catenin by their interaction, which promotes the transcription of cell migration related genes, including MMP7 and c-Myc. Furthermore, depletion of PKM2/beta-catenin abolished the migration effect of AMPK agonists, but did not affect their effects on suppression of cell proliferation. Our results provided a novel function of AMPK in cancer migration, and suggested that a combination of AMPK activation and PKM2 depletion or inhibition can be a new strategy to achieve better therapeutic effects for TC patients.