ArticleThe Journal of cell biology1999
R-Ras signals through specific integrin alpha cytoplasmic domains to promote migration and invasion of breast epithelial cells.
Article in The Journal of cell biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
68 citing papers in PubMed, 162 citations in OpenAlex.
- RRAS and RRAS2 Mutations Are Recurrent Oncogenic Drivers in Lung Cancer and Are Sensitive to the Pan-RAS Inhibitor RMC-6236.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Article
- The ancestral type of the R-RAS protein has oncogenic potential.Cellular & molecular biology letters · 2024Article
- Potential of Farnesyl Transferase Inhibitors in Combination Regimens in Squamous Cell Carcinomas.Cancers · 2021Article
- MicroRNA-34a activation in tuberous sclerosis complex during early brain development may lead to impaired corticogenesis.Neuropathology and applied neurobiology · 2021Article
- R-Ras subfamily proteins elicit distinct physiologic effects and phosphoproteome alterations in neurofibromin-null MPNST cells.Cell communication and signaling : CCS · 2021Article
- The Role of R-Ras Proteins in Normal and Pathologic Migration and Morphologic Change.The American journal of pathology · 2021Review
- Glycoproteomic analysis of the changes in protein N-glycosylation during neuronal differentiation in human-induced pluripotent stem cells and derived neuronal cells.Scientific reports · 2021Article
- Flightless anchors IQGAP1 and R-ras to mediate cell extension formation and matrix remodeling.Molecular biology of the cell · 2020Article
- BC200 overexpression contributes to luminal and triple negative breast cancer pathogenesis.BMC cancer · 2019Article
- Comparative Analysis of the Transcriptome and Proteome during Mouse Placental Development.Journal of proteome research · 2019Article
- M-Ras/Shoc2 signaling modulates E-cadherin turnover and cell-cell adhesion during collective cell migration.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- The leucine-rich region of Flightless I interacts with R-ras to regulate cell extension formation.Molecular biology of the cell · 2018Article
- Integrins promote axonal regeneration after injury of the nervous system.Biological reviews of the Cambridge Philosophical Society · 2018Review
- TC21/RRas2 regulates glycoprotein VI-FcRγ-mediated platelet activation and thrombus stability.Journal of thrombosis and haemostasis : JTH · 2018Article
- Regulation of H-Ras-driven MAPK signaling, transformation and tumorigenesis, but not PI3K signaling and tumor progression, by plasma membrane microdomains.Oncogenesis · 2016Article
- Structure, functional regulation and signaling properties of Rap2B.Oncology letters · 2016Article
- ARF-GEF cytohesin-2/ARNO regulates R-Ras and α5-integrin recycling through an EHD1-positive compartment.Molecular biology of the cell · 2015Article
- A short splicing isoform of afadin suppresses the cortical axon branching in a dominant-negative manner.Molecular biology of the cell · 2015Article
- NGF-induced TrkA/CD44 association is involved in tumor aggressiveness and resistance to lestaurtinib.Oncotarget · 2015Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Specificity and modulation of integrin function have important consequences for cellular responses to the extracellular matrix, including differentiation and transformation. The Ras-related GTPase, R-Ras, modulates integrin affinity, but little is known of the signaling pathways and biological functions downstream of R-Ras. Here we show that stable expression of activated R-Ras or the closely related TC21 (R-Ras 2) induced integrin-mediated migration and invasion of breast epithelial cells through collagen and disrupted differentiation into tubule structures, whereas dominant negative R-Ras had opposite effects. These results imply novel roles for R-Ras and TC21 in promoting a transformed phenotype and in the basal migration and polarization of these cells. Importantly, R-Ras induced an increase in cellular adhesion and migration on collagen but not fibronectin, suggesting that R-Ras signals to specific integrins. This was further supported by experiments in which R-Ras enhanced the migration of cells expressing integrin chimeras containing the alpha2, but not the alpha5, cytoplasmic domain. In addition, a transdominant inhibition previously noted only between integrin beta cytoplasmic domains was observed for the alpha2 cytoplasmic domain; alpha2beta1-mediated migration was inhibited by the expression of excess alpha2 but not alpha5 cytoplasmic domain-containing chimeras, suggesting the existence of limiting factors that bind the integrin alpha subunit. Using pharmacological inhibitors, we found that R-Ras induced migration on collagen through a combination of phosphatidylinositol 3-kinase and protein kinase C, but not MAPK, which is distinct from the other Ras family members, Rac, Cdc42, and N- and K-Ras. Thus, R-Ras communicates with specific integrin alpha cytoplasmic domains through a unique combination of signaling pathways to promote cell migration and invasion.
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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.