Endosomal membrane state governs trafficking and cell migration under TFEB control
- 1Institut Gustave Roussy
Abstract
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 depletion selectively impaired cell migration and adhesion. This phenotype was associated with the retention of the adhesion molecule integrin {beta}5 (ITG{beta}5), in central intracellular compartments identified as multivesicular bodies (MVBs) upon TFEB knockdown (KD). Mechanistically, TFEB regulated cellular lipid composition and membrane fluidity of acidic endosomes that controlled ITG{beta}5 trafficking. Remarkably, exogenous supplementation with a monounsaturated fatty acid (MUFA) that increased MVB membrane fluidity was sufficient to phenocopy the intracellular trapping of ITG{beta}5 in 2D culture and 3D tumoroids. We further showed that TFEB-dependent maintenance of MVB membrane fluidity relies on ESCRT-0 subcomplex, HGS/Hrs, which retains cholesterol at MVBs. Together, these findings reveal how transcriptional programs shape endosomal membrane states to control cargo trafficking and cell behavior.
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BibTeX
@misc{schauer2026endosomal,
title = {{Endosomal membrane state governs trafficking and cell migration under TFEB control}},
author = {K. Schauer and J. Patat and A. Mathey and E. OUNI and P. Mathur and H. Lachuer and N. Elkhatib and M. Khaled and G. Blivet-Bailly and A. Klymchenko and J. Sampaio},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.02.748843},
url = {https://www.biorxiv.org/content/10.64898/2026.09.02.748843v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Endosomal membrane state governs trafficking and cell migration under TFEB control
AU - K. Schauer
AU - J. Patat
AU - A. Mathey
AU - E. OUNI
AU - P. Mathur
AU - H. Lachuer
AU - N. Elkhatib
AU - M. Khaled
AU - G. Blivet-Bailly
AU - A. Klymchenko
AU - J. Sampaio
PY - 2026
DA - 2026/09/02
PB - bioRxiv
DO - 10.64898/2026.09.02.748843
UR - https://www.biorxiv.org/content/10.64898/2026.09.02.748843v1
AB - 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 depletion selectively impaired cell migration and adhesion. This phenotype was associated with the retention of the adhesion molecule integrin {beta}5 (ITG{beta}5), in central intracellular compartments identified as multivesicular bodies (MVBs) upon TFEB knockdown (KD). Mechanistically, TFEB regulated cellular lipid composition and membrane fluidity of acidic endosomes that controlled ITG{beta}5 trafficking. Remarkably, exogenous supplementation with a monounsaturated fatty acid (MUFA) that increased MVB membrane fluidity was sufficient to phenocopy the intracellular trapping of ITG{beta}5 in 2D culture and 3D tumoroids. We further showed that TFEB-dependent maintenance of MVB membrane fluidity relies on ESCRT-0 subcomplex, HGS/Hrs, which retains cholesterol at MVBs. Together, these findings reveal how transcriptional programs shape endosomal membrane states to control cargo trafficking and cell behavior.
ER -