ArticleProceedings of the National Academy of Sciences of the United States of America2023
Cancer-associated fibroblasts influence Wnt/PCP signaling in gastric cancer cells by cytoneme-based dissemination of ROR2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. 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, 44 citations in OpenAlex.
- Metabolic heterogeneity and functional diversity of cancer-associated fibroblasts in gastric cancer (Review).Oncology letters · 2026Review
- Regulation and function of specialized membrane protrusions in intercellular communication.Nature reviews. Molecular cell biology · 2026Review
- Emerging Roles of Cytoneme-Mediated Signaling in Cancer.International journal of molecular sciences · 2026Review
- Targeting frizzled receptors (FZDs) for anti-tumor therapy: From orthosteric to allosteric inhibition.Acta pharmaceutica Sinica. B · 2026Review
- Gastric Cancer: Pathobiology and Therapeutics.MedComm · 2026Review
- Review
- LncRNA NEAT1 promotes immunosuppression in gastric cancer under endoplasmic reticulum stress by maintaining the MMolecular cancer · 2026Article
- Stemness signatures reflect prognostic disturbances in gastric cancer.World journal of gastrointestinal oncology · 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
- Extracellular matrix: unlocking new avenues in cancer treatment.Biomarker research · 2025Review
- Making cells inter-connected for signaling communication: a developmental view of cytonemes.Cell communication and signaling : CCS · 2025Review
- The Drosophila epidermal growth factor receptor pathway regulates Hedgehog signalling and cytoneme behaviour.Nature communications · 2025Article
- Amyloid-β can activate JNK signalling via WNT5A-ROR2 to reduce synapse formation in Alzheimer's disease.Journal of cell science · 2025Article
- Mast cells: key players in digestive system tumors and their interactions with immune cells.Cell death discovery · 2025Review
- Unleashing Wnts: Wnt Ligands Fuel Cancer Spread.Journal of cancer biology · 2025Article
- Frizzled receptors: gatekeepers of Wnt signaling in development and disease.Frontiers in cell and developmental biology · 2025Review
- Aberrant Expression of JAM2 Inhibits Invasion and Migration in Lung Adenocarcinoma.Cancer reports (Hoboken, N.J.) · 2025Article
- WNT7A-positive dendritic cytonemes control synaptogenesis in cortical neurons.Development (Cambridge, England) · 2024Article
- Review
- Cancer-associated fibroblast-derived WNT5A promotes cell proliferation, metastasis, stemness and glycolysis in gastric cancer via regulating HK2.World journal of surgical oncology · 2024Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Cancer-associated fibroblasts (CAFs) are a crucial component in the tumor microenvironment influencing cancer progression. Besides shaping the extracellular matrix, these fibroblasts provide signaling factors to facilitate tumor survival and alter tumor behavior. In gastric cancer, one crucial signaling pathway influencing invasion and metastasis is the Wnt/Planar Cell Polarity (PCP) signaling. The crucial PCP ligand in this context is WNT5A, which is produced by the CAFs, and gastric cancer cells react upon this signal by enhanced polarized migration. Why gastric cancer cells respond to this signal is still unclear, as their expression level for the central WNT5A receptor, ROR2, is very low. Here, we show that CAFs display long and branched filopodia that form an extensive, complex network engulfing gastric cancer cells, such as the gastric cancer cell line AGS. CAFs have a significantly higher expression level of ROR2 than normal gastric fibroblasts and AGS cells. By high-resolution imaging, we observe a direct transfer of fluorescently tagged ROR2 from CAF to AGS cells by signaling filopodia, known as cytonemes. Surprisingly, we find that the transferred ROR2 complexes can activate Wnt/JNK signaling in AGS cells. Consistently, blockage of ROR2 function in the CAFs leads to reduced paracrine Wnt/JNK signaling, cell polarization, and migration of the receiving AGS cells. Complementary, enhanced migration via paracrine ROR2 transfer was observed in a zebrafish in vivo model. These findings demonstrate a fresh role for cytoneme-mediated signaling in the tumor microenvironment. Cytonemes convey Wnt receptors from CAFs to gastric cancer cells, allowing them to respond to Wnt/PCP signals.
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Registered trials
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