ArticleThe Journal of clinical investigation2024
Single-cell analysis of breast cancer metastasis reveals epithelial-mesenchymal plasticity signatures associated with poor outcomes.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- A predictive endocrine resistance index accurately stratifies luminal breast cancer treatment responders and nonresponders.The Journal of clinical investigation · 2025Trial
- An Anoikis-Related Gene Signature Associated With Stromal Remodeling and Clinical Outcome in Gastric Cancer.Chemical biology & drug design · 2026Article
- Metastasis of triple negative breast cancer is regulated by a targetable miR-342-E2F network.EMBO molecular medicine · 2026Article
- Adaptive epithelial-mesenchymal bi-directional transition: A key invasive plasticity for tumor metastasis.iScience · 2026Review
- Regulation of PSAT1 and PHGDH by m6A in endocrine-resistant breast cancer cells.Biochimica et biophysica acta. Molecular basis of disease · 2026Article
- Serum amyloid A1 promote progression of breast cancer and is associated with epithelial-mesenchymal transition.Translational cancer research · 2026Article
- Co-occurrence of transcriptionally distinct persister cell states underpins neoadjuvant therapy resistance in triple‑negative breast cancer.Genome medicine · 2026Article
- PMEPA1 modulates YAP1 nuclear translocation to disrupt EMT subtypes and promote metastasis in Biliary tract cancer.Cell death & disease · 2026Article
- Tumor Heterogeneity Induces Pro- and Anti-metastatic Myeloid Cell Phenotypes in Breast Cancer Lung Metastasis.bioRxiv : the preprint server for biology · 2026Article
- A highly resolved integrated single-cell atlas of human breast cancers.NAR genomics and bioinformatics · 2026Article
- LMO2 Regulates Epithelial-Mesenchymal Plasticity of Mammary Epithelial Cells.Journal of mammary gland biology and neoplasia · 2026Article
- Targeting tumor transition windows.Exploration of targeted anti-tumor therapy · 2026Review
- Single cell mapping of B and T cell dynamics in breast cancer lymph node metastasis.Frontiers in bioinformatics · 2026Article
- Evolution of Cancer Metastases via Lineage Trans-Differentiation.Research (Washington, D.C.) · 2026Article
- Circulating tumor cells as predictive biomarkers in the risk stratification of DCIS: Evidence of early dissemination.Science advances · 2025Article
- Role of intratumoral heterogeneity in metastatic progression and drug resistance.Discover oncology · 2025Review
- Molecular Mechanisms of Estrogens in the Induction of Epithelial-to-Mesenchymal Transition and Metastasis in Breast Cancer.International journal of molecular sciences · 2025Review
- MUW researcher of the month: Dr.in Juliane Winkler.Wiener klinische Wochenschrift · 2025Article
- Decoding metastatic microenvironments through single-cell omics reveals new insights into niche dynamics and tumor evolution.PLoS biology · 2025Article
- Integrating model systems and genomic insights to decipher mechanisms of cancer metastasis.Nature reviews. Genetics · 2025Review
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27 authors.
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Abstract
Metastasis is the leading cause of cancer-related deaths. It is unclear how intratumor heterogeneity (ITH) contributes to metastasis and how metastatic cells adapt to distant tissue environments. The study of these adaptations is challenged by the limited access to patient material and a lack of experimental models that appropriately recapitulate ITH. To investigate metastatic cell adaptations and the contribution of ITH to metastasis, we analyzed single-cell transcriptomes of matched primary tumors and metastases from patient-derived xenograft models of breast cancer. We found profound transcriptional differences between the primary tumor and metastatic cells. Primary tumors upregulated several metabolic genes, whereas motility pathway genes were upregulated in micrometastases, and stress response signaling was upregulated during progression. Additionally, we identified primary tumor gene signatures that were associated with increased metastatic potential and correlated with patient outcomes. Immune-regulatory control pathways were enriched in poorly metastatic primary tumors, whereas genes involved in epithelial-mesenchymal transition were upregulated in highly metastatic tumors. We found that ITH was dominated by epithelial-mesenchymal plasticity (EMP), which presented as a dynamic continuum with intermediate EMP cell states characterized by specific genes such as CRYAB and S100A2. Elevated expression of an intermediate EMP signature correlated with worse patient outcomes. Our findings identified inhibition of the intermediate EMP cell state as a potential therapeutic target to block metastasis.
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