ArticleProceedings of the National Academy of Sciences of the United States of America2017
Rab5-regulated endocytosis plays a crucial role in apical extrusion of transformed cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- Silencing the Signal: The Metastasis Suppressor NDRG1 Disrupts Small Extracellular Vesicle-Mediated Crosstalk in Pancreatic Cancer.Journal of extracellular vesicles · 2026Article
- CDK1-mediated phosphorylation of EPLIN is crucial for mitotic spindle positioning.Communications biology · 2026Article
- Rab5 nucleotide binding promotes oxidative metabolism to fuel hepatocellular carcinoma cell proliferation.The Journal of biological chemistry · 2026Article
- Non-canonical EGFR signaling promotes MAPK-dependent extrusion of epithelial cells.Journal of cell science · 2025Article
- Epithelial guardians against cancer: integrating cell competition and extrusion in early tumor control.Discover oncology · 2025Review
- KRASG12D Cells Override Homeostatic Cell Elimination Mechanisms in Adult Pancreas Via Wnt5a and Cell Dormancy.Gastroenterology · 2025Article
- Exploring the Enigma: The Role of the Epithelial Protein Lost in Neoplasm in Normal Physiology and Cancer Pathogenesis.International journal of molecular sciences · 2024Review
- Article
- Pleiotropic effects of cell competition between normal and transformed cells in mammalian cancers.Journal of cancer research and clinical oncology · 2023Review
- Aging dysregulates neutrophil extracellular trap formation in response to HIV in blood and genital tissues.Frontiers in immunology · 2023Article
- Characterization of LIMA1 and its emerging roles and potential therapeutic prospects in cancers.Frontiers in oncology · 2023Review
- CD147-spike protein interaction in COVID-19: Get the ball rolling with a novel receptor and therapeutic target.The Science of the total environment · 2022Review
- The role of tissue maturity and mechanical state in controlling cell extrusion.Current opinion in genetics & development · 2022Review
- Spike S1 domain interactome in non-pulmonary systems: A role beyond the receptor recognition.Frontiers in molecular biosciences · 2022Article
- Epithelial Protein Lost in Neoplasm, EPLIN, the Cellular and Molecular Prospects in Cancers.Biomolecules · 2021Review
- Adhesion-mediated heterogeneous actin organization governs apoptotic cell extrusion.Nature communications · 2021Article
- S100A8/A9 mediate the reprograming of normal mammary epithelial cells induced by dynamic cell-cell interactions with adjacent breast cancer cells.Scientific reports · 2021Article
- CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells.Signal transduction and targeted therapy · 2020Article
- Article
- Symmetry Breaking and Epithelial Cell Extrusion.Cells · 2020Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Newly emerging transformed cells are often eliminated from epithelial tissues. Recent studies have revealed that this cancer-preventive process involves the interaction with the surrounding normal epithelial cells; however, the molecular mechanisms underlying this phenomenon remain largely unknown. In this study, using mammalian cell culture and zebrafish embryo systems, we have elucidated the functional involvement of endocytosis in the elimination of RasV12-transformed cells. First, we show that Rab5, a crucial regulator of endocytosis, is accumulated in RasV12-transformed cells that are surrounded by normal epithelial cells, which is accompanied by up-regulation of clathrin-dependent endocytosis. Addition of chlorpromazine or coexpression of a dominant-negative mutant of Rab5 suppresses apical extrusion of RasV12 cells from the epithelium. We also show in zebrafish embryos that Rab5 plays an important role in the elimination of transformed cells from the enveloping layer epithelium. In addition, Rab5-mediated endocytosis of E-cadherin is enhanced at the boundary between normal and RasV12 cells. Rab5 functions upstream of epithelial protein lost in neoplasm (EPLIN), which plays a positive role in apical extrusion of RasV12 cells by regulating protein kinase A. Furthermore, we have revealed that epithelial defense against cancer (EDAC) from normal epithelial cells substantially impacts on Rab5 accumulation in the neighboring transformed cells. This report demonstrates that Rab5-mediated endocytosis is a crucial regulator for the competitive interaction between normal and transformed epithelial cells in mammals.
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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.