ArticleOncogene2017
Autocrine WNT2 signaling in fibroblasts promotes colorectal cancer progression.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 140 citations in OpenAlex.
- Cancer‑associated fibroblasts in human malignancies, with a particular emphasis on sarcomas (Review).International journal of oncology · 2025Review
- Retinal parameter analysis and diagnostic potentail exploration in familial exudative vitreoretinopathy using ultra-widefield fundus photography.International journal of retina and vitreous · 2025Article
- Expression of Lymphoid Enhancer-Binding Factor 1 in Cancer-Associated Fibroblasts Mediates Tumor Growth and Transdifferentiation Toward Squamous Cell Carcinoma in Human Breast Cancer.Cancer medicine · 2025Article
- Organotropic metastasis in colorectal cancer: integrating molecular pathways with therapeutic opportunities.Frontiers in immunology · 2025Review
- Neutrophil extracellular traps predict poor response and prognosis in non-small cell lung cancer immunotherapy.Therapeutic advances in medical oncology · 2025Article
- CYP2S1 Knockout Promotes Intestinal Tumor Growth inJournal of Cancer · 2025Article
- Interplay between cancer-associated fibroblasts and dendritic cells: implications for tumor immunity.Frontiers in immunology · 2025Review
- Current perspectives and trends in colorectal cancer and cancer-associated fibroblasts: a review and bibliometric analysis.Frontiers in immunology · 2025Review
- The Wnt/β-catenin signaling pathway in colorectal cancer: mechanism and intervention of traditional Chinese medicine and chemical compound.Frontiers in pharmacology · 2025Review
- Unleashing Wnts: Wnt Ligands Fuel Cancer Spread.Journal of cancer biology · 2025Article
- Unraveling the role of cancer-associated fibroblasts in colorectal cancer.World journal of gastrointestinal oncology · 2024Review
- FEV-mediated WNT2 transcription is involved in the progression of colorectal cancer via the Wnt signaling.Cytotechnology · 2024Article
- Regulation of intestinal epithelial homeostasis by mesenchymal cells.Inflammation and regeneration · 2024Review
- [Role of Abelson interactor 2 in progression and prognosis of gastric cancer and its regulatory mechanisms].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Investigating the effect of Fusobacterium nucleatum on the aggressive behavior of cancer-associated fibroblasts in colorectal cancer.Discover oncology · 2024Article
- Canonical WNT/β-catenin signaling upregulates aerobic glycolysis in diverse cancer types.Molecular biology reports · 2024Review
- Colorectal cancer cells secreting DKK4 transform fibroblasts to promote tumour metastasis.Oncogene · 2024Article
- Anti-angiogenesis in colorectal cancer therapy.Cancer science · 2024Review
- The Impact of Cancer-Associated Fibroblasts on the Biology and Progression of Colorectal Carcinomas.Genes · 2024Article
- The role of cancer-associated fibroblasts in the invasion and metastasis of colorectal cancer.Frontiers in cell and developmental biology · 2024Review
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 2 countries.
Funding
Abstract
The canonical WNT signaling pathway is crucial for intestinal stem cell renewal and aberrant WNT signaling is an early event in colorectal cancer (CRC) development. Here, we show for the first time that WNT2 is one of the most significantly induced genes in CRC stroma as compared to normal stroma. The impact of stromal WNT2 on carcinoma formation or progression was not addressed so far. Canonical WNT/β-catenin signaling was assessed using a 7TGP-reporter construct. Furthermore, effects of WNT2 on fibroblast migration and invasion were determined using siRNA-mediated gene silencing. Tumor cell invasion was studied using organotypic raft cultures and in vivo significance was assessed via a xenograft mouse model. We identified cancer-associated fibroblasts (CAFs) as the main source of WNT2. CAF-derived WNT2 activated canonical signaling in adenomatous polyposis coli/β-catenin wild-type colon cancer cells in a paracrine fashion, whereas no hyperactivation was detectable in cell lines harboring mutations in the adenomatous polyposis coli/β-catenin pathway. Furthermore, WNT2 activated autocrine canonical WNT signaling in primary fibroblasts, which was associated with a pro-migratory and pro-invasive phenotype. We identified FZD8 as the putative WNT2 receptor in CAFs. Three-dimensional organotypic co-culture assays revealed that WNT2-mediated fibroblast motility and extracellular matrix remodeling enhanced cancer cell invasion of cell lines even harboring mutations in the adenomatous polyposis coli/β-catenin pathway. Thus, suggesting a tumor-promoting influence on a broad range of CRC. In line, WNT2 also promotes tumor growth, invasion and metastasis in vivo. Moreover, high WNT2 expression is associated with poor prognosis in human CRC. The identification of the pro-malignant function of stromal derived WNT2 in CRC classifies WNT2 and its receptor as promising stromal targets to confine cancer progression in combination with conventional or targeted therapies.
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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.