ArticleCancer research2014
Small GTPase RhoE/Rnd3 is a critical regulator of Notch1 signaling.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- From Quiescence to Activation: The Reciprocal Regulation of Ras and Rho Signaling in Hepatic Stellate Cells.Cells · 2025Article
- Laminin α5: a key factor in tumor metastasis.Clinical & experimental metastasis · 2025Review
- RND3 Potentiates Proinflammatory Activation through NOTCH Signaling in Activated Macrophages.Journal of immunology research · 2024Article
- Decoding key cell sub-populations and molecular alterations in glioblastoma at recurrence by single-cell analysis.Acta neuropathologica communications · 2023Article
- Fibroblast-specific activation of Rnd3 protects against cardiac remodeling in diabetic cardiomyopathy via suppression of Notch and TGF-β signaling.Theranostics · 2022Article
- Inhibition of microRNA-128-3p alleviates liver ischaemia-reperfusion injury in mice through repressing the Rnd3/NF-Innate immunity · 2020Article
- Non-canonical Notch Signaling Regulates Actin Remodeling in Cell Migration by Activating PI3K/AKT/Cdc42 Pathway.Frontiers in pharmacology · 2019Article
- Genetic deletion ofOncotarget · 2017Article
- MicroRNAs in the etiology of colorectal cancer: pathways and clinical implications.Disease models & mechanisms · 2017Review
- RND3 promotes Snail 1 protein degradation and inhibits glioblastoma cell migration and invasion.Oncotarget · 2016Article
- Rnd3 as a Novel Target to Ameliorate Microvascular Leakage.Journal of the American Heart Association · 2016Article
- Pathophysiological Functions of Rnd3/RhoE.Comprehensive Physiology · 2015Review
- Downregulation of RND3/RhoE in glioblastoma patients promotes tumorigenesis through augmentation of notch transcriptional complex activity.Cancer medicine · 2015Article
- RhoE is required for contact inhibition and negatively regulates tumor initiation and progression.Oncotarget · 2015Article
- Inference of Low and High-Grade Glioma Gene Regulatory Networks Delineates the Role of Rnd3 in Establishing Multiple Hallmarks of Cancer.PLoS genetics · 2015Article
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Aberrations of Notch signaling have been implicated in a variety of human cancers. Oncogenic mutations in NOTCH1 are common in human T-cell leukemia and lymphomas. However, loss-of-function somatic mutations in NOTCH1 arising in solid tumors imply a tumor suppressor function, which highlights the need to understand Notch signaling more completely. Here, we describe the small GTPase RhoE/Rnd3 as a downstream mediator of Notch signaling in squamous cell carcinomas (SCC) that arise in skin epithelia. RhoE is a transcriptional target of activated Notch1, which is attenuated broadly in SCC cells. RhoE depletion suppresses Notch1-mediated signaling in vitro, rendering primary keratinocytes resistant to Notch1-mediated differentiation and thereby favoring a proliferative cell fate. Mechanistic investigations indicated that RhoE controls a key step in Notch1 signaling by mediating nuclear translocation of the activated portion of Notch1 (N1IC) through interaction with importins. Our results define RhoE as a Notch1 target that is essential for recruitment of N1IC to the promoters of Notch1 target genes, establishing a regulatory feedback loop in Notch1 signaling. This molecular circuitry may inform distinct cell fate decisions to Notch1 in epithelial tissues, where carcinomas such as SCC arise.
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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.