ArticleNPJ precision oncology2024
Cancer associated fibroblasts serve as an ovarian cancer stem cell niche through noncanonical Wnt5a signaling.
Article in NPJ precision oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 38 citations in OpenAlex.
- DCLK1 regulates stemness and IL-6/STAT3-dependent metastatic niche formation in chemoresistant ovarian cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Review
- DOCK1 inhibitor Box5 (TFA) suppresses proliferation of AML cell lines and prolongs survival in AML xenograft models.Scientific reports · 2026Article
- Wnt signaling and the tumor microenvironment: implications for cancer progression and therapeutics.Oncogene · 2026Review
- Balancing stromal-induced complexity in 3D ovarian cancer models through heterotypic co-culture with fibroblasts or architected micro-scaffolds.Journal of biological engineering · 2026Article
- Cell-intrinsic and tumor microenvironmental determinants of platinum resistance in epithelial ovarian cancer.Discover oncology · 2026Review
- Novel anti-tumor strategies: targeting the crosstalk between cancer stem cells and cancer-associated fibroblasts to resist drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Integrative transcriptomics and structure-based screening identifiesFrontiers in bioinformatics · 2026Article
- Targeting Ovarian Neoplasms: Subtypes and Therapeutic Options.Medicina (Kaunas, Lithuania) · 2025Review
- Modulation of Human Immune Cells by Propyl-Propane Thiosulfonate (PTSO) Inhibits Colorectal Tumor Progression in a Humanized Mouse Model.Nutrients · 2025Article
- Wnt/CaOncology letters · 2025Review
- Tumoroid model recreates clinically relevant phenotypes of high grade serous ovarian cancer (HGSC) cells, carcinoma associated fibroblasts, and macrophages.Research square · 2025Article
- Cancer-associated fibroblasts promote growth and dissemination of esophageal squamous cell carcinoma cells by secreting WNT family member 5A.Molecular and cellular biochemistry · 2025Article
- INHBABMC cancer · 2025Article
- Conserved spatial subtypes and cellular neighborhoods of cancer-associated fibroblasts revealed by single-cell spatial multi-omics.Cancer cell · 2025Article
- A comprehensive overview of ovarian cancer stem cells: correlation with high recurrence rate, underlying mechanisms, and therapeutic opportunities.Molecular cancer · 2025Review
- Article
- From Defense to Disease: How the Immune System Fuels Epithelial-Mesenchymal Transition in Ovarian Cancer.International journal of molecular sciences · 2025Review
- Decoding immune low-response states in ovarian cancer: insights from single-cell and spatial transcriptomics for precision immunotherapy.Frontiers in immunology · 2025Review
- The metabolic landscape of ovarian cancer stem cells: how do they survive?Frontiers in oncology · 2025Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Frequent relapse and chemoresistance cause poor outcome in ovarian cancer (OC) and cancer stem cells (CSCs) are important contributors. While most studies focus exclusively on CSCs, the role of the microenvironment in providing optimal conditions to maintain their tumor-initiating potential remains poorly understood. Cancer associated fibroblasts (CAFs) are a major constituent of the OC tumor microenvironment and we show that CAFs and CSCs are enriched following chemotherapy in patient tumors. CAFs significantly increase OC cell resistance to carboplatin. Using heterotypic CAF-OC cocultures and in vivo limiting dilution assay, we confirm that the CAFs act by enriching the CSC population. CAFs increase the symmetric division of CSCs as well as the dedifferentiation of bulk OC cells into CSCs. The effect of CAFs is limited to OC cells in their immediate neighborhood, which can be prevented by inhibiting Wnt. Analysis of single cell RNA-seq data from OC patients reveal Wnt5a as the highest expressed Wnt in CAFs and that certain subpopulations of CAFs express higher levels of Wnt5a. Our findings demonstrate that Wnt5a from CAFs activate a noncanonical Wnt signaling pathway involving the ROR2/PKC/CREB1 axis in the neighboring CSCs. While canonical Wnt signaling is found to be predominant in interactions between cancer cells in patients, non-canonical Wnt pathway is activated by the CAF-OC crosstalk. Treatment with a Wnt5a inhibitor sensitizes tumors to carboplatin in vivo. Together, our results demonstrate a novel mechanism of CSC maintenance by signals from the microenvironmental CAFs, which can be targeted to treat OC chemoresistance and relapse.
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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.