ArticleCancer research2009
Breast cancer migration and invasion depend on proteasome degradation of regulator of G-protein signaling 4.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
94 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.
- RGS Family Remodeling in Breast Cancer: A Meta-Analysis and Multi-Omics Profiling of Prognostic Biomarkers.Cancer medicine · 2026Pooled it
- Oxidative stress induced by DMSA-IONPs impairs breast cancer cell migration and paracrine cell communication.Journal of nanobiotechnology · 2026Article
- Exploring the relationship between Alzheimer's disease and colorectal/breast cancers using SEER database, Mendelian randomization, and transcriptomic data.Discover oncology · 2026Article
- Temporal dynamics of macrophage activation duringVirulence · 2025Article
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- Rac1 in gastric cancer: a molecular driver of invasion, EMT, and therapeutic resistance.Journal of translational medicine · 2025Review
- TRPM2 channels mediate ROS-induced actin remodeling and cell migration of prostate cancer cells.BMC cancer · 2025Article
- An mRNA-display derived cyclic peptide scaffold reveals the substrate binding interactions of an N-terminal cysteine oxidase.Nature communications · 2025Article
- CircWDR78 inhibits the development of colorectal cancer by regulating the miR-653-3p/RGS4 axis.Journal of cancer research and clinical oncology · 2025Article
- AGS3-based optogenetic GDI induces GPCR-independent Gβγ signalling and macrophage migration.Open biology · 2025Article
- Comprehensive single-cell aging atlas of healthy mammary tissues reveals shared epigenomic and transcriptomic signatures of aging and cancer.Nature aging · 2025Article
- Emerging regulators of gastric cancer angiogenesis: Synergistic effects of regulator of G protein signaling 4 and midkine.CytoJournal · 2025Article
- How mitochondrial dynamics imbalance affects the progression of breast cancer:a mini review.Medical oncology (Northwood, London, England) · 2024Review
- Ophiopogonin D' inhibited tumour growth and metastasis of anaplastic thyroid cancer by modulating JUN/RGS4 signalling.Journal of cellular and molecular medicine · 2024Article
- AGS3-based optogenetic GDI induces GPCR-independent Gβγ signaling and macrophage migration.bioRxiv : the preprint server for biology · 2024Article
- Aberrant non-canonical NF-κB signalling reprograms the epigenome landscape to drive oncogenic transcriptomes in multiple myeloma.Nature communications · 2024Article
- Identification of TFR2 as a novel ferroptosis‑related gene that serves an important role in prognosis and progression of triple‑negative breast cancer.Oncology letters · 2024Article
- Unraveling the prognostic significance of RGS gene family in gastric cancer and the potential implication of RGS4 in regulating tumor-infiltrating fibroblast.Frontiers in molecular biosciences · 2024Article
- Function and regulation of RGS family members in solid tumours: a comprehensive review.Cell communication and signaling : CCS · 2023Review
34 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
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Aberrant signaling through G-protein coupled receptors promotes metastasis, the major cause of breast cancer death. We identified regulator of G-protein signaling 4 (RGS4) as a novel suppressor of breast cancer migration and invasion, important steps of metastatic cascades. By blocking signals initiated through G(i)-coupled receptors, such as protease-activated receptor 1 and CXC chemokine receptor 4, RGS4 disrupted Rac1-dependent lamellipodia formation, a key step involved in cancer migration and invasion. RGS4 has GTPase-activating protein (GAP) activity, which inhibits G-protein coupled receptor signaling by deactivating G-proteins. An RGS4 GAP-deficient mutant failed to inhibit migration and invasion of breast cancer cells in both in vitro assays and a mouse xenograft model. Interestingly, both established breast cancer cell lines and human breast cancer specimens showed that the highest levels of RGS4 protein were expressed in normal breast epithelia and that RGS4 down-regulation by proteasome degradation is an index of breast cancer invasiveness. Proteasome blockade increased endogenous RGS4 protein to levels that markedly inhibit breast cancer cell migration and invasion, which was reversed by an RGS4-targeted short hairpin RNA. Our findings point to the existence of a mechanism for posttranslational regulation of RGS4 function, which may have important implications for the acquisition of a metastatic phenotype by breast cancer cells. Preventing degradation of RGS4 protein should attenuate aberrant signal inputs from multiple G(i)-coupled receptors, thereby retarding the spread of breast cancer cells and making them targets for surgery, radiation, and immune treatment.
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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.