ArticleMolecular biology of the cell2017
Phosphorylated cortactin recruits Vav2 guanine nucleotide exchange factor to activate Rac3 and promote invadopodial function in invasive breast cancer cells.
Article in Molecular biology of the cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- Membrane Curvature Activates Src kinase and Promotes Metastatic Cancer Cell Survival.bioRxiv : the preprint server for biology · 2026Article
- Deciphering the oncogenic role of Rac family small GTPase 3 in hepatocellular carcinoma through multiomics integration.World journal of hepatology · 2025Article
- Unravelling molecular dynamics in living cells: Fluorescent protein biosensors for cell biology.Journal of microscopy · 2025Review
- Identification and verification of anoikis-related gene markers to predict the prognosis of patients with bladder cancer and assist in the diagnosis and treatment of bladder cancer.Translational cancer research · 2024Article
- Scaffold protein SH3BP2 signalosome is pivotal for immune activation in nephrotic syndrome.JCI insight · 2024Article
- Early diagnosis and prognostic potential of RAC3 in bladder tumor.International urology and nephrology · 2024Article
- Role of anoikis-related gene RAC3 in prognosis, immune microenvironment, and contribution to malignant behaviorFrontiers in pharmacology · 2024Article
- YAP1 induces invadopodia formation by transcriptionally activating TIAM1 through enhancer in breast cancer.Oncogene · 2022Article
- RAC3 Inhibition Induces Autophagy to Impair Metastasis in Bladder Cancer CellsFrontiers in oncology · 2022Article
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- Fe65: A Scaffolding Protein of Actin Regulators.Cells · 2021Review
- CBP-JMF: An Improved Joint Matrix Tri-Factorization Method for Characterizing Complex Biological Processes of Diseases.Frontiers in genetics · 2021Article
- Prognostic model of 10 immune-related genes and identification of small molecule drugs in bladder urothelial carcinoma (BLCA).Translational andrology and urology · 2020Article
- Rho GTPases: Big Players in Breast Cancer Initiation, Metastasis and Therapeutic Responses.Cells · 2020Review
- Cortactin function in invadopodia.Small GTPases · 2020Review
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- Tumor Cellular and Microenvironmental Cues Controlling Invadopodia Formation.Frontiers in cell and developmental biology · 2020Review
- Targeting Rac and Cdc42 GEFs in Metastatic Cancer.Frontiers in cell and developmental biology · 2020Review
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
Breast carcinoma cells use specialized, actin-rich protrusions called invadopodia to degrade and invade through the extracellular matrix. Phosphorylation of the actin nucleation-promoting factor and actin-stabilizing protein cortactin downstream of the epidermal growth factor receptor-Src-Arg kinase cascade is known to be a critical trigger for invadopodium maturation and subsequent cell invasion in breast cancer cells. The functions of cortactin phosphorylation in this process, however, are not completely understood. We identify the Rho-family guanine nucleotide exchange factor Vav2 in a comprehensive screen for human SH2 domains that bind selectively to phosphorylated cortactin. We demonstrate that the Vav2 SH2 domain binds selectively to phosphotyrosine-containing peptides corresponding to cortactin tyrosines Y421 and Y466 but not to Y482. Mutation of the Vav2 SH2 domain disrupts its recruitment to invadopodia, and an SH2-domain mutant form of Vav2 cannot support efficient matrix degradation in invasive MDA-MB-231 breast cancer cells. We show that Vav2 function is required for promoting invadopodium maturation and consequent actin polymerization, matrix degradation, and invasive migratory behavior. Using biochemical assays and a novel Rac3 biosensor, we show that Vav2 promotes Rac3 activation at invadopodia. Rac3 knockdown reduces matrix degradation by invadopodia, whereas a constitutively active Rac3 can rescue the deficits in invadopodium function in Vav2-knockdown cells. Together these data indicate that phosphorylated cortactin recruits Vav2 to activate Rac3 and promote invadopodial maturation in invasive breast cancer cells.
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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.