ArticleCell communication and signaling : CCS2009
Rac1 activation inhibits E-cadherin-mediated adherens junctions via binding to IQGAP1 in pancreatic carcinoma cells.
Article in Cell communication and signaling : CCS, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 68 citations in OpenAlex.
- Programming Spatial Cell Sorting by Engineering Cadherin Intracellular Activity.ACS synthetic biology · 2024Article
- Tight junction protein cingulin variant is associated with cancer susceptibility by overexpressed IQGAP1 and Rac1-dependent epithelial-mesenchymal transition.Journal of experimental & clinical cancer research : CR · 2024Article
- Loss of cell-cell adhesion triggers cell migration through Rac1-dependent ROS generation.Life science alliance · 2023Article
- The role of cell division control protein 42 in tumor and non-tumor diseases: A systematic review.Journal of Cancer · 2022Review
- TBC1D2 Promotes Ovarian Cancer MetastasisFrontiers in oncology · 2022Article
- The Role of Heat Shock Protein 40 in Carcinogenesis and Biology of Colorectal Cancer.Current pharmaceutical design · 2022Review
- Review
- Role of IQGAP1 in Carcinogenesis.Cancers · 2021Review
- Article
- Integrative Analysis of the IQ Motif-Containing GTPase-Activating Protein Family Indicates That the IQGAP3-PIK3C2B Axis Promotes Invasion in Colon Cancer.OncoTargets and therapy · 2020Article
- RAC1-GTP promotes epithelial-mesenchymal transition and invasion of colorectal cancer by activation of STAT3.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- Ras GTPase-Activating-Like Protein IQGAP1 (IQGAP1) Promotes Breast Cancer Proliferation and Invasion and Correlates with Poor Clinical Outcomes.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Proteomic Characterization Reveals a Molecular Portrait of Nasopharyngeal Carcinoma Differentiation.Journal of Cancer · 2017Article
- The NKD1/Rac1 feedback loop regulates the invasion and migration ability of hepatocarcinoma cells.Scientific reports · 2016Article
- Anti-tumor efficacy of BEZ235 is complemented by its anti-angiogenic effects via downregulation of PI3K-mTOR-HIF1alpha signaling in HER2-defined breast cancers.American journal of cancer research · 2016Article
- The Transcriptional Repressor ZNF503/Zeppo2 Promotes Mammary Epithelial Cell Proliferation and Enhances Cell Invasion.The Journal of biological chemistry · 2015Article
- Rac1 expression in epithelial ovarian cancer: effect on cell EMT and clinical outcome.Medical oncology (Northwood, London, England) · 2015Article
- Ras-related C3 botulinum toxin substrate 1 activation is involved in the pathogenesis of diabetic retinopathy.Experimental and therapeutic medicine · 2015Article
- Btbd7 contributes to reduced E-cadherin expression and predicts poor prognosis in non-small cell lung cancer.BMC cancer · 2014Article
- A PAK6-IQGAP1 complex promotes disassembly of cell-cell adhesions.Cellular and molecular life sciences : CMLS · 2014Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMonomeric GTPases of the Rho family control a variety of cellular functions including actin cytoskeleton organisation, cell migration and cell adhesion. Defects in these regulatory processes are involved in tumour progression and metastasis. The development of metastatic carcinoma is accompanied by deregulation of adherens junctions, which are composed of E-cadherin/beta- and alpha-catenin complexes.
resultsHere, we show that the activity of the monomeric GTPase Rac1 contributes to inhibition of E-cadherin-mediated cell-cell adhesion in pancreatic carcinoma cells. Stable expression of constitutively active Rac1(V12) reduced the amount of E-cadherin on protein level in PANC-1 pancreatic carcinoma cells, whereas expression of dominant negative Rac1(N17) resulted in an increased amount of E-cadherin. Extraction of proteins associated with the actin cytoskeleton as well as coimmunoprecipitation analyses demonstrated markedly decreased amounts of E-cadherin/catenin complexes in Rac1(V12)-expressing cells, but increased amounts of functional E-cadherin/catenin complexes in cells expressing Rac1(N17). Cell aggregation and migration assays revealed, that cells containing less E-cadherin due to expression of Rac1(V12), exhibited reduced cell-cell adhesion and increased cell motility. The Rac/Cdc42 effector protein IQGAP1 has been implicated in regulating cell-cell adhesion. Coimmunoprecipitation studies showed a decrease in the association between IQGAP1 and beta-catenin in Rac1(V12)-expressing PANC-1 cells and an association of IQGAP1 with Rac1(V12). Elevated association of IQGAP1 with the E-cadherin adhesion complex via beta-catenin correlated with increased intercellular adhesion of PANC-1 cells.
conclusionThese results indicate that active Rac1 destabilises E-cadherin-mediated cell-cell adhesion in pancreatic carcinoma cells by interacting with IQGAP1 which is associated with a disassembly of E-cadherin-mediated adherens junctions. Inhibition of Rac1 activity induced increased E-cadherin-mediated cellular adhesion.
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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.