Biology subjects

Elkhatib, N.

Publications and source records attributed to Elkhatib, N..

3 recordsLinked to original sources

bioRxiv2026

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 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.

cell biology↗

bioRxiv2025

Associative memory in human cancer cells

In psychology and neuroscience, associative memory refers to the capacity to learn and remember a link between two unrelated items. Although associative memory is widely believed to be restricted to animals possessing a complex nervous system, several reports have suggested that single-cell organisms can be conditioned to develop an associative memory-like behavior. Here, we report that human cancer cell lines can be conditioned to associate an extracellular matrix component and Gefitinib, a drug that reduces cell migration velocity. Collagen-I was periodically paired with Gefitinib and we observed that conditioned cells progressive decreased migration velocity on collagen-I but not on other extracellular matrix components. We identified the adenosine receptor ADORA2A as a key actor regulating the acquisition of associative memory. We also observed that the magnitude of the conditioned response oscillated over time with the same periodicity as paired stimuli presentations during conditioning. We found that mitochondria morphology oscillated with the same periodicity, suggesting that memory and energy metabolisms are linked. We propose that human cancer cells can be conditioned to integrate a link between two stimuli from their environment in a process that may allow to anticipate future stress exposition.

cell biology↗

bioRxiv2019

Endocytosis frustration potentiates compression-induced receptor signaling

Cells experience mechanical stresses in different physiological and pathological settings. Clathrin-coated structures (CCSs) are sensitive to such perturbations in a way that often results in a mechanical impairment of their capacity to bud, ultimately impairing endocytosis. Compressive stress is a particular mechanical perturbation that leads to increased membrane tension and promotes proliferative signals. Here, we report that compression leads to CCSs frustration and that CCSs are required to potentiate receptor-mediated signaling in these conditions. We first confirmed that pressure stalls CCSs dynamics and showed that it also slows down the dynamic exchange of CCSs building blocks. As previously reported, compression-induced paracrine activation of the epidermal growth factor receptor (EGFR) was the primary cause of ERK activation in these conditions. We observed that the EGFR was efficiently recruited at CCSs upon compression and that CCSs were required for full ERK activation. In addition, we demonstrated that compression-induced frustrated CCSs could also serve as signaling platforms for the hepatocyte growth factor receptor (HGFR), provided HGF was present in the medium. We thus propose that, besides the particular case of EGFR paracrine activation, CCS frustration resulting from mechanical perturbations can potentiate signaling through different receptors with potential important consequences on cell adaptation to its environment.

cell biology↗