ArticleThe Journal of biological chemistry2010
The epsin family of endocytic adaptors promotes fibrosarcoma migration and invasion.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- RLIP76: a versatile ATP-dependent transporter as a pharmacotherapeutic target for epilepsy management.Inflammopharmacology · 2026Review
- A pan-cancer single-cell transcriptomic atlas of human bone metastases.Cell reports. Medicine · 2026Article
- Septin organization is regulated by the Gpa1 ubiquitination domain and endocytic machinery during the yeast pheromone response.Molecular biology of the cell · 2025Article
- Article
- Discovering Breast Cancer Biomarkers Candidates through mRNA Expression Analysis Based on The Cancer Genome Atlas Database.Journal of personalized medicine · 2022Article
- Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer's Disease?International journal of molecular sciences · 2022Review
- Fixing the GAP: The role of RhoGAPs in cancer.European journal of cell biology · 2022Review
- Article
- Epsin 3 potentiates the NF‑κB signaling pathway to regulate apoptosis in breast cancer.Molecular medicine reports · 2022Article
- Gene Signatures Induced by Ionizing Radiation as Prognostic Tools in an In Vitro Experimental Breast Cancer Model.Cancers · 2021Review
- RLIP76: A Structural and Functional Triumvirate.Cancers · 2021Review
- Epsins in vascular development, function and disease.Cellular and molecular life sciences : CMLS · 2021Review
- Epsins 1 and 2 promote NEMO linear ubiquitination via LUBAC to drive breast cancer development.The Journal of clinical investigation · 2021Article
- Murine Epsins Play an Integral Role in Podocyte Function.Journal of the American Society of Nephrology : JASN · 2020Article
- A self-sustaining endocytic-based loop promotes breast cancer plasticity leading to aggressiveness and pro-metastatic behavior.Nature communications · 2020Article
- Ral signaling pathway in health and cancer.Cancer medicine · 2017Review
- Article
- Genetic reduction of vascular endothelial growth factor receptor 2 rescues aberrant angiogenesis caused by epsin deficiency.Arteriosclerosis, thrombosis, and vascular biology · 2014Article
- RhoGTPase-binding proteins, the exocyst complex and polarized vesicle trafficking.Small GTPases · 2014Review
- The structure of the RLIP76 RhoGAP-Ral binding domain dyad: fixed position of the domains leads to dual engagement of small G proteins at the membrane.Structure (London, England : 1993) · 2013Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abnormalities in the process of endocytosis are classically linked to malignant transformation through the deficient down-regulation of signaling receptors. The present study describes a non-classical mechanism that does not require internalization by which endocytic proteins affect cell migration and basement membrane invasion. Specifically, we found that the endocytic adaptor epsin binds and regulates the biological properties of the signaling molecule RalBP1 (Ral-binding protein 1). Epsin interacted with the N terminus of RalBP1 via its characteristic epsin N-terminal homology (ENTH) domain. A combination of siRNA-mediated knock-down and transfection of siRNA-resistant constructs in fibrosarcoma cells demonstrated that impairment of the epsin-RalBP1 interaction led to cell migration and basement membrane invasion defects. We found the ENTH domain was necessary and sufficient to sustain normal cell migration and invasion. Because all the epsin endocytic motifs reside in the C-terminal part of the molecule, these results suggest that this novel regulatory circuit does not require endocytosis. In addition, cells depleted of epsin-RalBP1 complex displayed deficient activation of Rac1 and Arf6 suggesting a signaling function for this novel interaction. Further, overexpression of either epsin or RalBP1 enhanced migration and invasion of fibrosarcoma cells. Collectively, our results indicate that epsin regulates RalBP1 function in Rac1- and Arf6-dependent pathways to ultimately affect cell migration and invasion. We propose that the observed up-regulation of both epsin and RalBP1 in certain cancers contributes to their invasive characteristics.
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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.