ArticleThe Journal of clinical investigation2016
RB1 deficiency in triple-negative breast cancer induces mitochondrial protein translation.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 149 citations in OpenAlex.
- TFAP2B and FOXC1 are associated with biologically and clinically distinct differentiation states in triple-negative breast cancer.Scientific reports · 2026Article
- Assessing the significance of CCNE1 overexpression in triple negative breast cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- TLR7 signature of tumour innervation reveals two distinct pathways of triple-negative breast cancer progression.British journal of cancer · 2026Article
- Specialized high-capacity mitochondria fuel cell invasion.Current biology : CB · 2026Article
- Metabolic permissiveness: how tissue context shapes cancer.Genes & development · 2026Review
- Future perspective of clinical usefulness of metabolic and mitochondrial heterogeneity in triple-negative breast cancers.International journal of clinical oncology · 2025Review
- Potential Loss of Imprinting of Tumor Suppressor Gene RB1 in Triple Negative Breast Cancer.Breast cancer research : BCR · 2025Article
- Comparative genomic analysis of multiple mammary tumors from a single dog: whole-genome sequencing study.Irish veterinary journal · 2025Article
- The tumor suppressor pRb and its relative p130 are required to maintain murine adult skeletal muscle homeostasis.Oncogene · 2025Article
- RB1 controls differentiation through positive regulation of phosphoglycerate mutases.Cell death & disease · 2025Article
- Mitochondrial Translation Inhibition Uncovers a Critical Metabolic-Epigenetic Interface in Renal Cell Carcinoma.Metabolites · 2025Article
- Mitochondrial Translation Inhibition Uncovers a Critical Metabolic-Epigenetic Interface in Renal Cell Carcinoma.bioRxiv : the preprint server for biology · 2025Article
- Recent Advances in Pineoblastoma Research: Molecular Classification, Modelling and Targetable Vulnerabilities.Cancers · 2025Review
- Mitochondria in tumor immune surveillance and tumor therapies targeting mitochondria.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Loss of chromosome cytoband 13q14.2 orchestrates breast cancer pathogenesis and drug response.Breast cancer research : BCR · 2024Article
- Deregulation of mitochondrial gene expression in cancer: mechanisms and therapeutic opportunities.British journal of cancer · 2024Review
- The treatment landscape of triple-negative breast cancer.Medical oncology (Northwood, London, England) · 2024Review
- Tigecycline causes loss of cell viability mediated by mitochondrial OXPHOS and RAC1 in hepatocellular carcinoma cells.Journal of translational medicine · 2023Article
- Thinking (Metastasis) outside the (Primary Tumor) Box.Cancers · 2023Article
- Cyclic fasting bolsters cholesterol biosynthesis inhibitors' anticancer activity.Nature communications · 2023Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
Abstract
Triple-negative breast cancer (TNBC) includes basal-like and claudin-low subtypes for which no specific treatment is currently available. Although the retinoblastoma tumor-suppressor gene (RB1) is frequently lost together with TP53 in TNBC, it is not directly targetable. There is thus great interest in identifying vulnerabilities downstream of RB1 that can be therapeutically exploited. Here, we determined that combined inactivation of murine Rb and p53 in diverse mammary epithelial cells induced claudin-low-like TNBC with Met, Birc2/3-Mmp13-Yap1, and Pvt1-Myc amplifications. Gene set enrichment analysis revealed that Rb/p53-deficient tumors showed elevated expression of the mitochondrial protein translation (MPT) gene pathway relative to tumors harboring p53 deletion alone. Accordingly, bioinformatic, functional, and biochemical analyses showed that RB1-E2F complexes bind to MPT gene promoters to regulate transcription and control MPT. Additionally, a screen of US Food and Drug Administration-approved (FDA-approved) drugs identified the MPT antagonist tigecycline (TIG) as a potent inhibitor of Rb/p53-deficient tumor cell proliferation. TIG preferentially suppressed RB1-deficient TNBC cell proliferation, targeted both the bulk and cancer stem cell fraction, and strongly attenuated xenograft growth. It also cooperated with sulfasalazine, an FDA-approved inhibitor of cystine xCT antiporter, in culture and xenograft assays. Our results suggest that RB1 deficiency promotes cancer cell proliferation in part by enhancing mitochondrial function and identify TIG as a clinically approved drug for RB1-deficient TNBC.
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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.