LAUSR

OBJECTIVE To investigate the effect of AMPK on tight junction (TJ) components, ZO-1 and F-actin, and the underlying mechanisms of AMPK in inhibiting migration of tongue squamous cell carcinoma (TSCC) cells. METHODS Expression and distribution of mRNA and/or protein was detected by qRT-PCR, western blot or immunofluorescence. The migration ability was tested by scratch and transwell migration assays. Transient knockdown of ZO-1 was achieved by siRNA transfection. RESULTS AMPK can be activated within both short-time (90 min) and long-time (24 or 48 h) treatment with AICAR. Cell migration was inhibited after AMPK activation. ZO-1 was translocated from cytoplasm to perimembrane and distributed continuously after short-time activation of AMPK. However, the continuous distribution of ZO-1 was broken up after long-time activation of AMPK, as well as F-actin, accompanied by shortened and decreased filopodia. ZO-1 expression and Cofilin activity was upregulated by long-time activation of AMPK, and the inhibitory effect on migration and upregulation of Cofilin activity of AMPK was partially reversed by knockdown of ZO-1. CONCLUSIONS AICAR induced activation of AMPK could greatly damage to the structure of TJ and inhibited the migration of TSCC cells through the abnormal increase and redistribution of ZO-1 and ZO-1/Cofilin mediated depolymerization of F-actin.