ArticleCell2021
Spliceosome-targeted therapies trigger an antiviral immune response in triple-negative breast cancer.
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Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers.
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146citing papers in PubMed
13.6field-weighted citation impact, top 1% of its field
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Who cites it
146 citing papers in PubMed, 208 citations in OpenAlex.
- Sitravatinib plus tislelizumab in locally recurrent or metastatic triple-negative breast cancer: a multi-cohort, single-arm, phase II clinical trial (SPARK Trial).Molecular cancer · 2025Trial
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- Distinguishing self from non-self RNA by editing-specific inosine patterns.Nucleic acids research · 2026Article
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- MERTK inhibition cooperates with immunomodulatory cyclophosphamide to induce CXCL9⁺ monocyte-macrophage programming and durable antitumor immunity in triple negative breast cancer.Cancer immunology research · 2026Article
- Caspase-3 regulates RNA splicing and mitochondrial dynamics in microglia during Parkinson's disease.Cell death & disease · 2026Article
- IP-LC-MS/MS-Based Identification of Candidate TPL2 (MAP3K8)-Associated Proteins in Porcine PK-15 Cells.Journal of mass spectrometry : JMS · 2026Article
- Tumor cell intrinsic dsRNA innate immune response triggered by PARP inhibitor is compromised in BRCA1-deficient breast cancer by repressing IRF3.Protein & cell · 2026Article
- Inhibition of RNA splicing is a novel therapeutic strategy for disruption of nuclear replicating viruses.bioRxiv : the preprint server for biology · 2026Article
- The emerging roles of alternative splicing in modulating tumor immune responses and immunotherapies.Cell death and differentiation · 2026Review
- In vivo CRISPR screens identify CBX4 as an epigenetic regulator for cancer immunotherapy.The Journal of clinical investigation · 2026Article
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- Mitochondrial double-stranded RNA fuels pancreatic cancer growth via RIG-I/TLR3 inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- RNA-binding proteins and ribonucleoproteins as determinants of immunity.Nature reviews. Immunology · 2026Review
- Defects in intron recycling suppress the antiviral response via a mechanism of intronic endogenous dsRNA.The Journal of experimental medicine · 2026Article
- Integrative CRISPR Screening and RNA Analyses Discover an Essential Role for PUF60 Interactions with 3' Splice Sites in Cancer Progression.Cancer research · 2026Article
- LBR and LAP2 mediate heterochromatin tethering to the nuclear periphery to preserve genome homeostasis.Nature cell biology · 2026Article
- A Yeast-Based High-Throughput Screening Platform for the Discovery of Novel pre-mRNA Splicing Modulators.ACS chemical biology · 2026Article
86 more citing papers are in PubMed but not listed here.
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Authors and funding
37 authors at 1 institution in 1 country.
Elizabeth A BowlingVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Jarey H WangVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030, USA.
Fade GongVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
William WuVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030, USA.
Nicholas J NeillDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Ik Sun KimLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
Siddhartha TyagiVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Mayra OrellanaVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Sarah J KurleyVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Rocio Dominguez-VidañaDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Hsiang-Ching ChungVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Tiffany Y-T HsuVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030, USA.
Julien DubrulleDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Alexander B SaltzmanVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Heyuan LiVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Jitendra K MeenaVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Gino M CanlasVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Srinivas ChamakuriDepartment of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Swarnima SinghLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
Lukas M SimonTherapeutic Innovation Center, Baylor College of Medicine, Houston, TX 77030, USA.
Calla M OlsonTherapeutic Innovation Center, Baylor College of Medicine, Houston, TX 77030, USA.
Lacey E DobroleckiLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
Michael T LewisLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Bing ZhangDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Ido GoldingVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Jeffrey M RosenDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Damian W YoungDepartment of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030, USA; Therapeutic Innovation Center, Baylor College of Medicine, Houston, TX 77030, USA.
Anna MalovannayaVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Fabio StossiDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
George MilesLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Matthew J EllisLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Lihua YuH3Biomedicine, Cambridge, MA 02139, USA.
Silvia BuonamiciH3Biomedicine, Cambridge, MA 02139, USA.
Charles Y LinDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Therapeutic Innovation Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Kristen L KarlinTherapeutic Innovation Center, Baylor College of Medicine, Houston, TX 77030, USA.
Xiang H-F ZhangLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Thomas F WestbrookVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Therapeutic Innovation Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: thomasw@bcm.edu.
Baylor College of Medicine · US
Funding
Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI DAVID R ROWLEY · 2007 to 2026
$73.9MTissue Analysis & Molecular Imaging CoreP30DK056338 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI Geoffrey A Preidis · 2001 to 2026
$28.3MMICROSCALED PROTEOGENOMICS FOR CANCER CLINICAL TRIALSU01CA214125 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ANURAG, MEENAKSHI, CARR, STEVEN A · 2017 to 2021
$7.0MTherapeutic Targeting of RNA Splicing in Triple-Negative Breast CancerR01CA215226 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Thomas Westbrook · 2018 to 2026
$5.6MGENE REGULATION IN PHAGE LAMBDA: A REAL-TIME STUDY WITH SINGLE-EVENT RESOLUTIONR01GM082837 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI GOLDING, IDO · 2008 to 2020
$4.0MIdentifying and Targeting Onocgenic MYC Enhancer Control in Pediatric TumorsR01CA215452 · NCI · BAYLOR COLLEGE OF MEDICINE · PI WESTBROOK, THOMAS · 2017 to 2021
$2.0MTraining Interdisciplinary Pharmacology ScientistsT32GM120011 · NIGMS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI DESSAUER, CARMEN W. · 2016 to 2020
$1.0MCancer Research UK 27144Cancer Research UK C5470/A27144NCI NIH HHS P30 CA125123NCI NIH HHS R01 CA215226NCI NIH HHS R01 CA215452NCI NIH HHS U01 CA214125NIDDK NIH HHS P30 DK056338NIGMS NIH HHS R01 GM082837NIGMS NIH HHS T32 GM120011
Abstract
Many oncogenic insults deregulate RNA splicing, often leading to hypersensitivity of tumors to spliceosome-targeted therapies (STTs). However, the mechanisms by which STTs selectively kill cancers remain largely unknown. Herein, we discover that mis-spliced RNA itself is a molecular trigger for tumor killing through viral mimicry. In MYC-driven triple-negative breast cancer, STTs cause widespread cytoplasmic accumulation of mis-spliced mRNAs, many of which form double-stranded structures. Double-stranded RNA (dsRNA)-binding proteins recognize these endogenous dsRNAs, triggering antiviral signaling and extrinsic apoptosis. In immune-competent models of breast cancer, STTs cause tumor cell-intrinsic antiviral signaling, downstream adaptive immune signaling, and tumor cell death. Furthermore, RNA mis-splicing in human breast cancers correlates with innate and adaptive immune signatures, especially in MYC-amplified tumors that are typically immune cold. These findings indicate that dsRNA-sensing pathways respond to global aberrations of RNA splicing in cancer and provoke the hypothesis that STTs may provide unexplored strategies to activate anti-tumor immune pathways.
Indexed as
Adaptive ImmunityAnimalsApoptosisCell Line, TumorCytoplasmFemaleGene AmplificationHumansImmunityIntronsMiceMolecular Targeted TherapyProto-Oncogene Proteins c-mycRNA, Double-StrandedRNA SplicingSignal TransductionMYC protein, humanProto-Oncogene Proteins c-mycRNA, Double-Strandedanti-cancer immunityantiviral immunitydouble-stranded RNAMYConcogenic stressRNA splicing in cancerspliceosome-targeted therapiestriple-negative breast cancerviral mimicry
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