ArticleProceedings of the National Academy of Sciences of the United States of America2013
Paracrine Wnt signaling both promotes and inhibits human breast tumor growth.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 81 citations in OpenAlex.
- DP103 as a critical modulator of Wnt signaling and cancer stemness: implications for precision treatment in triple negative breast cancer.Cell death & disease · 2026Article
- KRT17 promotes triple negative breast cancer through activation of Wnt signaling and γδ T-cells recruitment.Communications biology · 2026Article
- Post-diagnostic statin use and breast cancer-specific mortality: a population-based cohort study.Breast cancer research and treatment · 2023Article
- Interplay between Signaling Pathways and Tumor Microenvironment Components: A Paradoxical Role in Colorectal Cancer.International journal of molecular sciences · 2023Review
- Exploration of cancer associated fibroblasts phenotypes in the tumor microenvironment of classical and pleomorphic Invasive Lobular Carcinoma.Frontiers in oncology · 2023Article
- Role of microRNA/lncRNA Intertwined With the Wnt/β-Catenin Axis in Regulating the Pathogenesis of Triple-Negative Breast Cancer.Frontiers in pharmacology · 2022Review
- Non-coding RNA-related antitumor mechanisms of marine-derived agents.Frontiers in pharmacology · 2022Review
- Association of statin use with clinical outcomes in patients with triple-negative breast cancer.Cancer · 2021Article
- Opposing effects of Wnt/β-catenin signaling on epithelial and mesenchymal cell fate in the developing cochlea.Development (Cambridge, England) · 2021Article
- Cancer-associated fibroblast-derived SDF-1 induces epithelial-mesenchymal transition of lung adenocarcinoma via CXCR4/β-catenin/PPARδ signalling.Cell death & disease · 2021Article
- Cancer-Associated Fibroblast Subgroups Showing Differential Promoting Effect on HNSCC Progression.Cancers · 2021Article
- Cancer-Associated Fibroblast Heterogeneity: A Factor That Cannot Be Ignored in Immune Microenvironment Remodeling.Frontiers in immunology · 2021Review
- Review
- Wnt activation as a therapeutic strategy in medulloblastoma.Nature communications · 2020Article
- WNT: an unexpected tumor suppressor in medulloblastoma.Molecular & cellular oncology · 2020Article
- Aberrant WNT/CTNNB1 Signaling as a Therapeutic Target in Human Breast Cancer: Weighing the Evidence.Frontiers in cell and developmental biology · 2020Review
- Wnt Binding Affinity Prediction for Putative Frizzled-Type Cysteine-Rich Domains.International journal of molecular sciences · 2019Article
- Review
- The MMTV-Wnt1 murine model produces two phenotypically distinct subtypes of mammary tumors with unique therapeutic responses to an EGFR inhibitor.Disease models & mechanisms · 2019Article
- Vitamin D and Wnt3A have additive and partially overlapping modulatory effects on gene expression and phenotype in human colon fibroblasts.Scientific reports · 2019Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Wnt signaling in mouse mammary development and tumorigenesis has been heavily studied and characterized, but its role in human breast cancer remains elusive. Although Wnt inhibitors are in early clinical development, it is unclear whether they will be of therapeutic benefit to breast cancer patients, and subsequently, to which ones. To address this, we generated a panel of Wnt reporting human breast cancer cell lines and identified a previously unrecognized enrichment for the ability to respond to Wnt in the basal B or claudin-low subtype, which has a poor prognosis and no available targeted therapies. By co-injecting Wnt3A expressing human mammary fibroblasts with human breast cancer cell lines into mouse mammary fat pads, we showed that elevated paracrine Wnt signaling was correlated with accelerated tumor growth. Using this heterotypic system and a dual lentiviral reporter system that enables simultaneous real-time measurement of both Wnt-responsive cells and bulk tumor cells, we analyzed the outcome of elevated Wnt signaling in patient-derived xenograft (PDX) models. Interestingly, the PDX models exhibited responses not observed in the cell lines analyzed. Exogenous WNT3A promoted tumor growth in one human epidermal growth factor receptor 2-overexpressing PDX line but inhibited growth in a second PDX line obtained from a patient with triple-negative breast cancer. Tumor suppression was associated with squamous differentiation in the latter. Thus, our work suggests that paracrine Wnt signaling can either fuel or repress the growth of human breast cancers depending on yet to be determined aspects of the molecular pathways they express.
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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.