ArticleDevelopmental cell2013
Dynamin 2 potentiates invasive migration of pancreatic tumor cells through stabilization of the Rac1 GEF Vav1.
Article in Developmental cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 74 citations in OpenAlex.
- Trial
- PACSIN2 regulates mercaptopurine cytotoxicity and cellular biomechanics through Rac1 modulation in intestinal epithelial cells.Frontiers in pharmacology · 2026Article
- RBMS1-HSPA8 axis activation drives head and neck squamous cell carcinoma progression.BMC cancer · 2025Article
- Pristimerin Promotes Ubiquitination of HSPA8 and Activates the VAV1/ERK Pathway to Suppress TNBC Proliferation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Nuclear Expression of Dynamin 2 Is Associated With Tumor Aggressiveness in Bladder Cancer Patients: A Bioinformatics and Experimental Approach.Cancer reports (Hoboken, N.J.) · 2024Article
- Inverted apicobasal polarity in health and disease.Journal of cell science · 2024Review
- Heat shock protein family A member 8 serving as a co-activator of transcriptional factor ETV4 up-regulates PHLDA2 to promote the growth of liver cancer.Acta pharmacologica Sinica · 2023Article
- Ectopic expression of DOCK8 regulates lysosome-mediated pancreatic tumor cell invasion.Cell reports · 2023Article
- Review
- The Cell Biology of Metastatic Invasion in Pancreatic Cancer: Updates and Mechanistic Insights.Cancers · 2023Review
- Development of versatile allele-specific siRNAs able to silence all the dominant dynamin 2 mutations.Molecular therapy. Nucleic acids · 2022Article
- Structural Analysis of Mitochondrial Dynamics-From Cardiomyocytes to Osteoblasts: A Critical Review.International journal of molecular sciences · 2022Review
- Overexpression of cytoplasmic dynamin 2 is associated with worse outcomes in patients with clear cell renal cell carcinoma.Cancer biomarkers : section A of Disease markers · 2022Article
- Beta-Pix-dynamin 2 complex promotes colorectal cancer progression by facilitating membrane dynamics.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- Role of Endocytosis Proteins in Gefitinib-Mediated EGFR Internalisation in Glioma Cells.Cells · 2021Article
- A review of Dynamin 2 involvement in cancers highlights a promising therapeutic target.Journal of experimental & clinical cancer research : CR · 2021Review
- Metastasis-suppressor NME1 controls the invasive switch of breast cancer by regulating MT1-MMP surface clearance.Oncogene · 2021Article
- Dysfunction of chaperone-mediated autophagy in human diseases.Molecular and cellular biochemistry · 2021Review
- The EphA4 Signaling is Anti-catabolic in Synoviocytes but Pro-anabolic in Articular Chondrocytes.Calcified tissue international · 2020Article
- Extracellular Vesicles (EVs) and Pancreatic Cancer: From the Role of EVs to the Interference with EV-Mediated Reciprocal Communication.Biomedicines · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The large GTPase Dynamin 2 (Dyn2) is markedly upregulated in pancreatic cancer, is a potent activator of metastatic migration, and is required for Rac1-mediated formation of lamellipodia. Here we demonstrate an unexpected mechanism of Dyn2 action in these contexts via direct binding to the Rac1 guanine nucleotide exchange factor (GEF) Vav1. Surprisingly, disruption of the Dyn2-Vav1 interaction targets Vav1 to the lysosome for degradation via an interaction with the cytoplasmic chaperone Hsc70, resulting in a dramatic reduction of Vav1 protein stability. Importantly, a specific mutation in Vav1 near its Dyn2-binding C-terminal Src homology 3 (SH3) domain prevents Hsc70 binding, resulting in a stabilization of Vav1 levels. Dyn2 binding regulates the interaction of Vav1 with Hsc70 to control the stability and subsequent activity of this oncogenic GEF. These findings elucidate how Dyn2 activates Rac1, lamellipod protrusion, and invasive cellular migration and provide insight into how this specific Vav is ectopically expressed in pancreatic tumors.
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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.