ArticleCell death & disease2022
Loss of function of BRCA1 promotes EMT in mammary tumors through activation of TGFβR2 signaling pathway.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Comparative analysis of distinct genomic landscapes in young-onset gBRCA1/2 breast cancer.JCI insight · 2026Article
- Interdependent roles of BRCA1, CtBP, estrogen, and NADH/NAD+ ratio in error-prone repair, breast cancer initiation, and metastasis.Molecular biology reports · 2026Review
- Harnessing transcriptional regulation of alternative end-joining to predict cancer treatment.NAR cancer · 2025Article
- Endothelial-to-Mesenchymal Transition in Cardiovascular Pathophysiology.International journal of molecular sciences · 2024Review
- 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
- Ribonucleotide reductase M2 (RRM2): Regulation, function and targeting strategy in human cancer.Genes & diseases · 2024Review
- A genetic mosaic mouse model illuminates the pre-malignant progression of basal-like breast cancer.Disease models & mechanisms · 2023Article
- Article
- miR-17-5p slows progression of hepatocellular carcinoma by downregulating TGFβR2.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- p18INK4C and BRCA1 inhibit follicular cell proliferation and dedifferentiation in thyroid cancer.Cell cycle (Georgetown, Tex.) · 2023Article
- Loss of function of GATA3 regulates FRA1 and c-FOS to activate EMT and promote mammary tumorigenesis and metastasis.Cell death & disease · 2023Article
- Therapeutic targeting approach on epithelial-mesenchymal plasticity to combat cancer metastasis.Medical oncology (Northwood, London, England) · 2023Review
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BRCA1 deficient breast cancers are aggressive and chemoresistant due, in part, to their enrichment of cancer stem cells that can be generated from carcinoma cells by an epithelial-mesenchymal transition (EMT). We previously discovered that BRCA1 deficiency activates EMT in mammary tumorigenesis. How BRCA1 controls EMT and how to effectively target BRCA1-deficient cancers remain elusive. We analyzed murine and human tumors and identified a role for Tgfβr2 in governing the molecular aspects of EMT that occur with Brca1 loss. We utilized CRISPR to delete Tgfβr2 and specific inhibitors to block Tgfβr2 activity and followed up with the molecular analysis of assays for tumor growth and metastasis. We discovered that heterozygous germline deletion, or epithelia-specific deletion of Brca1 in mice, activates Tgfβr2 signaling pathways in mammary tumors. BRCA1 depletion promotes TGFβ-mediated EMT activation in cancer cells. BRCA1 binds to the TGFβR2 locus to repress its transcription. Targeted deletion or pharmaceutical inhibition of Tgfβr2 in Brca1-deficient tumor cells reduces EMT and suppresses tumorigenesis and metastasis. BRCA1 and TGFβR2 expression levels are inversely related in human breast cancers. This study reveals for the first time that a targetable TGFβR signaling pathway is directly activated by BRCA1-deficiency in the induction of EMT in breast cancer progression.
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