ArticleCell death & disease2021
Decreased PRC2 activity supports the survival of basal-like breast cancer cells to cytotoxic treatments.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- MUC1 as a Survival Effector of Radiotherapy-Induced Epithelial Hybrid States in Basal-Like Breast Cancer.International journal of cancer · 2026Article
- Profiling the Complexity of Resistance Factors in Cancer Cells Towards Berberine and Its Derivatives.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Precision epigenetic therapies in oncology.Cancer metastasis reviews · 2025Review
- PCIF1 drives oesophageal squamous cell carcinoma progression via m6Am-mediated suppression of MTF2 translation.Clinical and translational medicine · 2025Article
- Polycomb repressive complex 2 (PRC2) pathway's role in cancer cell plasticity and drug resistance.Functional & integrative genomics · 2025Review
- Article
- Pharmacological Advancements of PRC2 in Cancer Therapy: A Narrative Review.Life (Basel, Switzerland) · 2024Review
- Nuclear Factor of Activated T Cells (NFAT) Proteins as Targeted Molecules in Diseases: A Narrative Review.Cureus · 2024Review
- The PRC2.1 Subcomplex Opposes G1 Progression through Regulation of CCND1 and CCND2.bioRxiv : the preprint server for biology · 2024Article
- Interpreting the molecular mechanisms of RBBP4/7 and their roles in human diseases (Review).International journal of molecular medicine · 2024Review
- RNF40 epigenetically modulates glycolysis to support the aggressiveness of basal-like breast cancer.Cell death & disease · 2023Article
- Tissue-Specific Tumour Suppressor and Oncogenic Activities of the Polycomb-like Protein MTF2.Genes · 2023Review
- Ezh2 promotes mammary tumor initiation through epigenetic regulation of the Wnt and mTORC1 signaling pathways.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Review
- ROBO3s: a novel ROBO3 short isoform promoting breast cancer aggressiveness.Cell death & disease · 2022Article
- HDAC8 suppresses the epithelial phenotype and promotes EMT in chemotherapy-treated basal-like breast cancer.Clinical epigenetics · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Breast cancer (BC) is the most common cancer occurring in women but also rarely develops in men. Recent advances in early diagnosis and development of targeted therapies have greatly improved the survival rate of BC patients. However, the basal-like BC subtype (BLBC), largely overlapping with the triple-negative BC subtype (TNBC), lacks such drug targets and conventional cytotoxic chemotherapies often remain the only treatment option. Thus, the development of resistance to cytotoxic therapies has fatal consequences. To assess the involvement of epigenetic mechanisms and their therapeutic potential increasing cytotoxic drug efficiency, we combined high-throughput RNA- and ChIP-sequencing analyses in BLBC cells. Tumor cells surviving chemotherapy upregulated transcriptional programs of epithelial-to-mesenchymal transition (EMT) and stemness. To our surprise, the same cells showed a pronounced reduction of polycomb repressive complex 2 (PRC2) activity via downregulation of its subunits Ezh2, Suz12, Rbbp7 and Mtf2. Mechanistically, loss of PRC2 activity leads to the de-repression of a set of genes through an epigenetic switch from repressive H3K27me3 to activating H3K27ac mark at regulatory regions. We identified Nfatc1 as an upregulated gene upon loss of PRC2 activity and directly implicated in the transcriptional changes happening upon survival to chemotherapy. Blocking NFATc1 activation reduced epithelial-to-mesenchymal transition, aggressiveness, and therapy resistance of BLBC cells. Our data demonstrate a previously unknown function of PRC2 maintaining low Nfatc1 expression levels and thereby repressing aggressiveness and therapy resistance in BLBC.
Indexed as
Identifiers
What OpenQuestion holds
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.