ArticleNucleic acids research2021
Loss of MED12 activates the TGFβ pathway to promote chemoresistance and replication fork stability in BRCA-deficient cells.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 25 citations in OpenAlex.
- Antitumor activity and structure-activity relationship of poly (ADP-ribose) polymerase (PARP)-based dual inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- CCNE1 overexpression drives a cGAS-STING-dependent interferon response and sensitizes HRD-positive ovarian cancer to immune checkpoint blockade.Journal for immunotherapy of cancer · 2026Article
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- Non-canonical subunit functions in multiprotein complexes: insights from the Mediator complex.Biochemical Society transactions · 2026Review
- The nuclease EXO1 promotes genomic instability by degrading nascent DNA in BRCA-proficient cells.Nature communications · 2026Article
- Genome-wide CRISPR screens identify the EXO1-CAF-1 pathway suppressing R-loop-associated DNA damage.Nucleic acids research · 2026Article
- Navigating PARP Inhibitor Resistance in Ovarian Cancer: Bridging Mechanistic Insights To Clinical Translation.Current treatment options in oncology · 2025Review
- MED12 mutation induces RTK inhibitor resistance in NSCLC via MEK/ERK pathway activation by inflammatory cytokines.Cellular and molecular life sciences : CMLS · 2025Article
- MED12 dysregulation: insights into cancer and therapeutic resistance.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Case Report: Atypical Nodular Dermatofibrosis and Renal Cysts in a Bichon Frise with a BRCA2 Mutation and No FLCN Mutation.Animals : an open access journal from MDPI · 2025Article
- Clinical approaches to overcome PARP inhibitor resistance.Molecular cancer · 2025Review
- CRISPR knockout genome-wide screens identify the HELQ-RAD52 axis in regulating the repair of cisplatin-induced single-stranded DNA gaps.Nucleic acids research · 2024Article
- PARP10 promotes the repair of nascent strand DNA gaps through RAD18 mediated translesion synthesis.Nature communications · 2024Article
- Uncovering miRNA-mRNA Regulatory Networks Related to Olaparib Resistance and Resensitization ofCells · 2024Article
- NEAT1 repression by MED12 creates chemosensitivity in p53 wild-type breast cancer cells.The FEBS journal · 2024Article
- CRISPR knockout genome-wide screens identify the HELQ-RAD52 axis in regulating the repair of cisplatin-induced single stranded DNA gaps.bioRxiv : the preprint server for biology · 2024Article
- USP1-dependent nucleolytic expansion of PRIMPOL-generated nascent DNA strand discontinuities during replication stress.Nucleic acids research · 2024Article
- Deficiency of Cbfβ in articular cartilage leads to osteoarthritis-like phenotype through Hippo/Yap, TGFβ, and Wnt/β-catenin signaling pathways.International journal of biological sciences · 2024Article
- A novel RBBP8(p.E281*) germline mutation is a predisposing mutation in familial hereditary cancer syndrome.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Molecular Pathways and Mechanisms of TGFβ in Cancer Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Understanding chemoresistance mechanisms in BRCA-deficient cells will allow for identification of biomarkers for predicting tumor response to therapy, as well as the design of novel therapeutic approaches targeting this chemoresistance. Here, we show that the protein MED12, a component of the Mediator transcription regulation complex, plays an unexpected role in regulating chemosensitivity in BRCA-deficient cells. We found that loss of MED12 confers resistance to cisplatin and PARP inhibitors in both BRCA1- and BRCA2-deficient cells, which is associated with restoration of both homologous recombination and replication fork stability. Surprisingly, MED12-controlled chemosensitivity does not involve a function of the Mediator complex, but instead reflects a distinct role of MED12 in suppression of the TGFβ pathway. Importantly, we show that ectopic activation of the TGFβ pathway is enough to overcome the fork protection and DNA repair defects of BRCA-mutant cells, resulting in chemoresistance. Our work identifies the MED12-TGFβ module as an important regulator of genomic stability and chemosensitivity in BRCA-deficient cells.
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Registered trials
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