ArticleThe Journal of clinical investigation2021
RGS2-mediated translational control mediates cancer cell dormancy and tumor relapse.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 44 papers.
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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
44 citing papers in PubMed, 47 citations in OpenAlex.
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- TRIM21-mediated ubiquitination of PARP1 regulated by the PI3K/AKT-STAT5A axis suppresses small cell lung cancer.Nature communications · 2026Article
- RGS19 drives tumor progression and immunosuppression in clear cell renal cell carcinoma by modulating CAMs and EMT.World journal of surgical oncology · 2026Article
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- Regulating the dormancy of cancer stem cells: a novel approach to preventing cancer relapse.Cell death & disease · 2026Review
- Secretory Lysosome-Related Gene Signature Defines the Immune Microenvironment and Identifies RGS2 as a Prometastatic Factor in Hepatocellular Carcinoma.Human mutation · 2026Article
- The enigmatic role of tumor dormancy cells in gynecologic cancers.Frontiers in immunology · 2026Review
- Cancer-specific bivalent promoters featuring low-level H3K27me3 signals favor active transcription and govern the cancer cell state transition.Acta biochimica et biophysica Sinica · 2025Article
- Unlocking Lung Cancer Cell Dormancy: An Epigenetic Perspective.International journal of molecular sciences · 2025Review
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- Understanding Tumor Dormancy: from Experimental Models to Mechanisms and Therapeutic Strategies.Biomolecules & therapeutics · 2025Review
- Integrated Single-Cell RNA-Seq Reveals Immunosuppressive Mechanisms of Treg Cell Differentiation and Tumor Microenvironment Interactions in Colorectal Cancer.Cancer medicine · 2025Article
- Diapause and Anoxia-Induced Quiescence Are Unique States in Embryos of the Annual Killifish,Biomolecules · 2025Article
- Nerve Growth Factor Signaling Promotes Nuclear Translocation of TRAF4 to Enhance Tumor Stemness and Metastatic Dormancy Via C-Jun-mediated IL-8 Autocrine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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- Review
- Compressive stresses in cancer: characterization and implications for tumour progression and treatment.Nature reviews. Cancer · 2024Review
- Integrated analysis of bulk and single-cell RNA-seq data reveals cell differentiation-related subtypes and a scoring system in bladder cancer.Journal of cellular and molecular medicine · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Slow-cycling/dormant cancer cells (SCCs) have pivotal roles in driving cancer relapse and drug resistance. A mechanistic explanation for cancer cell dormancy and therapeutic strategies targeting SCCs are necessary to improve patient prognosis, but are limited because of technical challenges to obtaining SCCs. Here, by applying proliferation-sensitive dyes and chemotherapeutics to non-small cell lung cancer (NSCLC) cell lines and patient-derived xenografts, we identified a distinct SCC subpopulation that resembled SCCs in patient tumors. These SCCs displayed major dormancy-like phenotypes and high survival capacity under hostile microenvironments through transcriptional upregulation of regulator of G protein signaling 2 (RGS2). Database analysis revealed RGS2 as a biomarker of retarded proliferation and poor prognosis in NSCLC. We showed that RGS2 caused prolonged translational arrest in SCCs through persistent eukaryotic initiation factor 2 (eIF2α) phosphorylation via proteasome-mediated degradation of activating transcription factor 4 (ATF4). Translational activation through RGS2 antagonism or the use of phosphodiesterase 5 inhibitors, including sildenafil (Viagra), promoted ER stress-induced apoptosis in SCCs in vitro and in vivo under stressed conditions, such as those induced by chemotherapy. Our results suggest that a low-dose chemotherapy and translation-instigating pharmacological intervention in combination is an effective strategy to prevent tumor progression in NSCLC patients after rigorous chemotherapy.
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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.