ArticleMolecular cancer research : MCR2014
TGFβ induces "BRCAness" and sensitivity to PARP inhibition in breast cancer by regulating DNA-repair genes.
Article in Molecular cancer research : MCR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 71 citations in OpenAlex.
- BET inhibition disrupts the FOXM1-MYC axis to induce BRCAness and enhance PARP inhibitor response.NPJ precision oncology · 2026Article
- Homologous recombination pathway alterations in basal-like breast cancer.Frontiers in oncology · 2026Review
- NEIL3 and TOP2A as key drivers of esophageal cancer through WNT signaling.Biomolecules & biomedicine · 2025Article
- Different Mechanisms in Doxorubicin-Induced Neurotoxicity: Impact of BRCA Mutations.International journal of molecular sciences · 2025Review
- Review
- Genome-wide in vivo CRISPR screen identifies TGFβ3 as actionable biomarker of palbociclib resistance in triple negative breast cancer.Molecular cancer · 2024Article
- PALB2-mutated human mammary cells display a broad spectrum of morphological and functional abnormalities induced by increased TGFβ signaling.Cellular and molecular life sciences : CMLS · 2024Article
- Targeting the Cdc2-like kinase 2 for overcoming platinum resistance in ovarian cancer.MedComm · 2024Article
- Shake It Up Baby Now: The Changing Focus on TWIST1 and Epithelial to Mesenchymal Transition in Cancer and Other Diseases.International journal of molecular sciences · 2023Review
- TGFβ signaling links early life endocrine-disrupting chemicals exposure to suppression of nucleotide excision repair in rat myometrial stem cells.Cellular and molecular life sciences : CMLS · 2023Article
- Article
- AKT2-mediated nuclear deformation leads to genome instability during epithelial-mesenchymal transition.iScience · 2023Article
- TGFβ signaling links early-life endocrine-disrupting chemicals exposure to suppression of nucleotide excision repair in rat myometrial stem cells.Research square · 2023Article
- PARP Inhibitors and Proteins Interacting with SLX4.Cancers · 2023Review
- Initiation phase cellular reprogramming ameliorates DNA damage in the ERCC1 mouse model of premature aging.Frontiers in aging · 2023Article
- The BRCAness Landscape of Cancer.Cells · 2022Article
- Assessment of the TGFB1 gene expression and methylation status of the promoter region in patients with colorectal cancer.Scientific reports · 2022Article
- Improved loss-of-function CRISPR-Cas9 genome editing in human cells concomitant with inhibition of TGF-β signaling.Molecular therapy. Nucleic acids · 2022Article
- A Lack of Effectiveness in the ATM-Orchestrated DNA Damage Response Contributes to the DNA Repair Defect of HPV-Positive Head and Neck Cancer Cells.Frontiers in oncology · 2022Article
- Breast Cancer Stem-Like Cells in Drug Resistance: A Review of Mechanisms and Novel Therapeutic Strategies to Overcome Drug Resistance.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
unlabelledTransforming growth factor beta (TGFβ) proteins are multitasking cytokines, in which high levels at tumor sites generally correlate with poor prognosis in human patients with cancer. Previously, it was reported that TGFβ downregulates the expression of ataxia telangiectasia-mutated (ATM) and mutS homolog 2 (MSH2) in breast cancer cells through an miRNA-mediated mechanism. In this study, expression of a panel of DNA-repair genes was examined, identifying breast cancer 1, early onset (BRCA1) as a target downregulated by TGFβ through the miR181 family. Correlations between the expression levels of TGFβ1 and the miR181/BRCA1 axis were observed in primary breast tumor specimens. By downregulating BRCA1, ATM, and MSH2, TGFβ orchestrates DNA damage response in certain breast cancer cells to induce a "BRCAness" phenotype, including impaired DNA-repair efficiency and synthetic lethality to the inhibition of poly (ADP-ribose) polymerase (PARP). Xenograft tumors with active TGFβ signaling exhibited resistance to the DNA-damaging agent doxorubicin but increased sensitivity to the PARP inhibitor ABT-888. Combination of doxorubicin with ABT-888 significantly improved the treatment efficacy in TGFβ-active tumors. Thus, TGFβ can induce "BRCAness" in certain breast cancers carrying wild-type BRCA genes and enhance the responsiveness to PARP inhibition, and the molecular mechanism behind this is characterized. IMPLICATIONS: These findings enable better selection of patients with sporadic breast cancer for PARP interventions, which have exhibited beneficial effects in patients carrying BRCA mutations.
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