ArticleScience advances2015
Regulated lysosomal exocytosis mediates cancer progression.
Article in Science advances, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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Who cites it
115 citing papers in PubMed, 158 citations in OpenAlex.
- Pathogen subversion of neuro-epidermal signaling impairs lysosomal function to disrupt collagen homeostasis in Caenorhabditis elegans.PLoS biology · 2026Article
- Loading is not delivering: Intracellular drug retention and migration capacity govern macrophage-based drug delivery.Science advances · 2026Article
- Pathogen Subversion of Neuro-Epidermal Signaling Impairs Lysosomal Function to Disrupt Collagen Homeostasis.bioRxiv : the preprint server for biology · 2026Article
- The endosteal niche regulates breast cancer cell dormancy in bone: identification of new molecular determinants.Bone research · 2026Article
- A non-enzymatic function of neuraminidase 1 restrains hepatic glucagon response in mice.Nature communications · 2026Article
- Article
- Oxidative stress induced by DMSA-IONPs impairs breast cancer cell migration and paracrine cell communication.Journal of nanobiotechnology · 2026Article
- Unraveling Lysosomal Exocytosis: From Molecular Mechanisms to Physiological Functions.Traffic (Copenhagen, Denmark) · 2026Review
- Lysosomal membrane permeabilization is involved in CYP2E1-induced apoptosis in hepatocellular carcinoma cells.BBA advances · 2026Article
- Membrane Merger Dynamics in Exocytosis and Endocytosis.Advances in experimental medicine and biology · 2026Review
- Nanosecond pulsed electric fields induce cell-size-dependent selective permeabilization of urothelial cancer cells.Communications biology · 2025Article
- Mechanistic insights into the dynamics of plasma membrane repair in cancer.Molecular biology reports · 2025Review
- Epididymal epithelial cells facilitate NEU1 loading to modulate sperm α-2,6 sialylation, enhance maturation and motility.Cellular and molecular life sciences : CMLS · 2025Article
- Nortriptyline Inhibits Lysosomal Exocytosis-Mediated SASP During Gastric Cancer Progression via Targeting HOXA1-PITX2 Phase Separation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Lysosome heterogeneity and diversity mapped through its distinct cellular functions.Cellular and molecular life sciences : CMLS · 2025Review
- Possible Roles for Purinergic Receptor P2RX4 in Breast and Prostate Cancers.International journal of molecular sciences · 2025Review
- From mitochondrial dysregulation to ferroptosis: Exploring new strategies and challenges in radioimmunotherapy (Review).International journal of oncology · 2025Review
- Epidrug screening identifies type I PRMT inhibitors as modulators of lysosomal exocytosis and drug sensitivity in cancers.Cell death & disease · 2025Article
- Multi-omics reveals that ST6GAL1 promotes colorectal cancer progression through LGALS3BP sialylation.Biomolecules & biomedicine · 2025Article
- Review
55 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Understanding how tumor cells transition to an invasive and drug-resistant phenotype is central to cancer biology, but the mechanisms underlying this transition remain unclear. We show that sarcomas gain these malignant traits by inducing lysosomal exocytosis, a ubiquitous physiological process. During lysosomal exocytosis, the movement of exocytic lysosomes along the cytoskeleton and their docking at the plasma membrane involve LAMP1, a sialylated membrane glycoprotein and target of the sialidase NEU1. Cleavage of LAMP1 sialic acids by NEU1 limits the extent of lysosomal exocytosis. We found that by down-regulation of NEU1 and accumulation of oversialylated LAMP1, tumor cells exacerbate lysosomal exocytosis of soluble hydrolases and exosomes. This facilitates matrix invasion and propagation of invasive signals, and purging of lysosomotropic chemotherapeutics. In Arf (-⁄-) mice, Neu1 haploinsufficiency fostered the development of invasive, pleomorphic sarcomas, expressing epithelial and mesenchymal markers, and lysosomal exocytosis effectors, LAMP1 and Myosin-11. These features are analogous to those of metastatic, pleomorphic human sarcomas, where low NEU1 levels correlate with high expression of lysosomal exocytosis markers. In a therapeutic proof of principle, we demonstrate that inhibiting lysosomal exocytosis reversed invasiveness and chemoresistance in aggressive sarcoma cells. Thus, we reveal that this unconventional, lysosome-regulated pathway plays a primary role in tumor progression and chemoresistance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.