Key Role of TFEB Nucleus Translocation for Silver Nanoparticle-Induced Cytoprotective Autophagy

Transcription factor EB (TFEB) is a master regulator of autophagy and lysosomal biogenesis. Here, silver nanoparticles (Ag NPs)-induced cytoprotective autophagy required TFEB is shown. Ag NPs-induced nucleus translocation of TFEB through a well-established mechanism involving dephosphorylation of TFEB at serine-142 and serine-211 but independent of both the mTORC1 and ERK1/2 pathways. TFEB nucleus translocation precedes autophagy induced by Ag NPs and leads to enhanced expression of autophagy-essential genes. Knocking down the expression of TFEB attenuates the autophagy induction is demonstrated, and in the meantime, enhanced cell killing in HeLa cells treats with Ag NPs, indicating that TFEB is the key mediator for Ag NPs-induced cytoprotective autophagy. The results pinpoint TFEB as a potential target for developing more effective Ag NPs-based cancer therapeutics.