Endosomal membrane state governs trafficking and cell migration under TFEB control
Transcription Factor EB (TFEB) regulates the biogenesis of lysosomes, which are acidic organelles of the endosomal network. While its role in cellular clearance is well established, the pleiotropic functions of TFEB across diverse cellular processes, as well as its activation in several cancer types, remain incompletely understood. Investigating TFEB in a bladder cancer model, we found that its…
TFEB, a transcription factor, governs the biogenesis of lysosomes, which are acidic organelles within the endosomal network. TFEB's role in cellular clearance is well-documented, but its impact on cellular processes, particularly in cancer, is not fully understood. In a bladder cancer model, researchers observed that TFEB depletion impaired cell migration and adhesion, with adhesion molecule integrin beta5 (ITGbeta5) retention in intracellular compartments called multivesicular bodies (MVBs).
TFEB regulates the lipid composition and membrane fluidity of acidic endosomes, which in turn controls ITGbeta5 trafficking. Supplementing with a monounsaturated fatty acid (MUFA) increased MVB membrane fluidity, trapping ITGbeta5 and reproducing the observed cellular phenotype. TFEB's maintenance of MVB membrane fluidity relies on the ESCRT-0 subcomplex, specifically HGS/Hrs, which retains cholesterol within the MVBs.
These findings reveal the transcriptional programs that shape endosomal membrane states to control cargo trafficking and cell behavior.
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