We demonstrate that TGF-β treatment leads to TFEB-driven autophagy, which is required for the migration and metastasis of PC cells due to TFEB-mediated endocytosis of Itgα5β1 and focal adhesion disassembly via transcriptional activating the RAB5A gene controlled by the CLEAR network. This evidence concerns the gene RAB5A and pachyonychia congenita.