We provide evidence that TFEB-driven autophagy is required for TGF-β-induced migration and metastasis of PC cells, because autophagy modulating effects of TFEB is in charge of endocytosis of Itgα5β1 and focal adhesion disassembly through RAB5A transcriptional activation controlled by the CLEAR network in PC cells. Here, TFEB is linked to pachyonychia congenita.