ArticleOncogene2017
The focal adhesion-associated proteins DOCK5 and GIT2 comprise a rheostat in control of epithelial invasion.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- A nomogram integrating mutation signatures and clinical features for prognostic stratification in bladder cancer.Discover oncology · 2025Article
- Visualizing fatigue mechanisms in non-communicable diseases: an integrative approach with multi-omics and machine learning.BMC medical informatics and decision making · 2025Article
- Rac1 Suppression by the Focal Adhesion Protein GIT ArfGAP2 and Podocyte Protection.Journal of the American Society of Nephrology : JASN · 2025Article
- Multi-omic and spatial analysis of mouse kidneys highlights sex-specific differences in gene regulation across the lifespan.Nature genetics · 2025Article
- Regulation of microtubule nucleation in glioblastoma cells by ARF GTPase-activating proteins GIT1 and GIT2 and protein kinase C.Cancer cell international · 2025Article
- Dock5 Deficiency Promotes Proteinuric Kidney Diseases via Modulating Podocyte Lipid Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- p120 RasGAP and ZO-2 are essential for Hippo signaling and tumor-suppressor function mediated by p190A RhoGAP.Cell reports · 2023Article
- Automated assembly of molecular mechanisms at scale from text mining and curated databases.Molecular systems biology · 2023Article
- Article
- Understanding the development of oral epithelial organs through single cell transcriptomic analysis.Development (Cambridge, England) · 2022Article
- Identifying common transcriptome signatures of cancer by interpreting deep learning models.Genome biology · 2022Article
- The anti-Rac1-GTP antibody and the detection of active Rac1: a tool with a fundamental flaw.Small GTPases · 2022Article
- Variable Distribution of DOCK-D Proteins between Cytosol and Nucleoplasm in Cell Lines, Effect of Interleukin-4 on DOCK10 in B-Cell Lymphoid Neoplasms, and Validation of a New DOCK10 Antiserum for Immunofluorescence Studies.Antibodies (Basel, Switzerland) · 2021Article
- Cryo-EM structure of the human ELMO1-DOCK5-Rac1 complex.Science advances · 2021Article
- Proteomic, biomechanical and functional analyses define neutrophil heterogeneity in systemic lupus erythematosus.Annals of the rheumatic diseases · 2021Article
- Evaluation of active Rac1 levels in cancer cells: A case of misleading conclusions from immunofluorescence analysis.The Journal of biological chemistry · 2020Article
- p190A RhoGAP induces CDH1 expression and cooperates with E-cadherin to activate LATS kinases and suppress tumor cell growth.Oncogene · 2020Article
- Exposure to environmental bisphenol A inhibits HTR-8/SVneo cell migration and invasion.Journal of biomedical research · 2020Article
- DOCK5 regulates energy balance and hepatic insulin sensitivity by targeting mTORC1 signaling.EMBO reports · 2020Article
- The Role of ARF Family Proteins and Their Regulators and Effectors in Cancer Progression: A Therapeutic Perspective.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
DOCK proteins are guanine nucleotide exchange factors for Rac and Cdc42 GTPases. DOCK1 is the founding member of the family and acts downstream of integrins via the canonical Crk-p130Cas complex to activate Rac GTPases in numerous contexts. In contrast, DOCK5, which possesses the greatest similarity to DOCK1, remains sparingly studied. Here we establish that DOCK5 has a non-redundant role in regulating motile and invasive capacities of epithelial cells. DOCK1 is constitutively associated with sites of integrin attachment termed focal adhesions (FAs). In contrast, we demonstrate that DOCK5 recruitment to FAs in Hela cells is restricted by GIT2, an established regulator of FA signaling. We determine that GIT2 is targeted to FAs in response to Rho-ROCK signaling and actomyosin contractility. Accordingly, inhibition of ROCK activity or MLC function promotes enrichment of DOCK5 in membrane protrusions and nascent cell-substratum adhesions. We further demonstrate that GIT2 inhibits the interaction of DOCK5 with Crk. Moreover, we show that depletion of GIT2 promotes DOCK5-dependent activation of the Crk-p130Cas signaling cascade to promote Rac1-mediated lamellipodial protrusion and FA turnover. The antagonism between GIT2 and DOCK5 extends to non-transformed MCF10A mammary epithelial cells, with DOCK5 'dialing-up' and GIT2 'dialing-down' invasiveness. Finally, we determine that DOCK5 inhibition attenuates invasion and metastasis of MDA-MB-231 cells and prolongs life span of mice injected with these cells. Collectively, our work identifies DOCK5 as a key regulator of epithelial invasion and metastasis, and demonstrates that suppression of DOCK5 by GIT2 represents a previously unappreciated mechanism for coordination of Rho and Rac GTPases.
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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.