ArticleCancer medicine2019
Cancer-associated fibroblasts secrete Wnt2 to promote cancer progression in colorectal cancer.
Article in Cancer medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed.
- Determinants of response and molecular dynamics in HER2+ER+ breast cancers from the NA-PHER2 trial receiving HER2-targeted and endocrine therapies.Nature communications · 2025Trial
- Cellular crosstalk of fibroblast-myofibroblast transition in intestinal homeostasis and disease.Biomarker research · 2026Review
- Potentially functional variants of Wnt signaling pathway genes predict risk of primary lung cancer in Chinese Han population.Scientific reports · 2026Article
- In vivo exposure to CXCL12-high CAFs and chronic CXCL12 stimulation in vitro is sufficient to enhance metastasis of ER-positive breast cancer.Breast cancer research and treatment · 2026Article
- S100A8/A9 as a key player in colorectal cancer: from diagnosis to therapeutic targeting.Frontiers in pharmacology · 2026Review
- Implantation of engineered adipocytes suppresses tumor progression in cancer models.Nature biotechnology · 2025Article
- Cancer‑associated fibroblasts in human malignancies, with a particular emphasis on sarcomas (Review).International journal of oncology · 2025Review
- The Significance of the Wnt/β-Catenin Pathway and Related Proteins in Gastrointestinal Malignancies.International journal of molecular sciences · 2025Review
- Alternative Splicing of FBLN2 Generates a Prometastatic Extracellular Matrix in Gastrointestinal Cancers by Determining N-Glycosylation of Fibulin 2.Genes to cells : devoted to molecular & cellular mechanisms · 2025Article
- Role of the Wnt signaling pathway in the complex microenvironment of breast cancer and prospects for therapeutic potential (Review).International journal of oncology · 2025Review
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Tenascin-C Potentiates Wnt Signaling in Thyroid Cancer.Endocrinology · 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
- Current perspectives and trends in colorectal cancer and cancer-associated fibroblasts: a review and bibliometric analysis.Frontiers in immunology · 2025Review
- Unleashing Wnts: Wnt Ligands Fuel Cancer Spread.Journal of cancer biology · 2025Article
- Organotropic metastasis in colorectal cancer: integrating molecular pathways with therapeutic opportunities.Frontiers in immunology · 2025Review
- Revisiting the role of cancer-associated fibroblasts in tumor microenvironment.Frontiers in immunology · 2025Review
- Frizzled receptors: gatekeepers of Wnt signaling in development and disease.Frontiers in cell and developmental biology · 2025Review
- GPA33 expression in colorectal cancer can be induced by WNT inhibition and targeted by cellular therapy.Oncogene · 2025Article
- Unraveling the role of cancer-associated fibroblasts in colorectal cancer.World journal of gastrointestinal oncology · 2024Review
4 more citing papers are in PubMed but not listed here.
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11 authors.
Funding
Abstract
Recent studies have shown that the tumor microenvironment plays a significant role in the progression of solid tumors. As an abundant component of the tumor microenvironment, cancer-associated fibroblasts (CAFs) have been shown to promote tumorigenesis and cancer aggressiveness, but their molecular characteristics remain poorly understood. In the present study, paired CAFs and normal fibroblasts (NFs) were isolated from five colorectal cancer (CRC) tissues from patients who underwent surgical resection. The gene expression profiles of CAFs and NFs identified by RNA sequencing were compared to understand the complex role of CAFs in cancer progression. Gene Set Enrichment Analysis revealed that the gene sets related to the Wnt signaling pathway were highly enriched in CAFs, as well as TGFβ signaling, which is considered to be a regulator of CAFs. Among the components of this pathway, Wnt2 was specifically expressed. The observations led us to speculate that Wnt2 is extremely involved in regulating CRC progression by CAFs. Thus, we performed immunohistochemical analysis on Wnt2 in 171 patients who underwent surgery for colorectal adenocarcinoma. Positive staining for Wnt2 was mainly observed in cancer stroma, although the immunoreactivity was weak in cancer cells. Wnt2 expression in CAFs was significantly correlated with depth of tumor (P < .001), lymph node metastasis (P = .044), TNM stage (P = .010), venous invasion (P < .001), and recurrence (P = .013). Subsequent in vitro analyses were conducted using conditioned medium (CM) from immortalized CAFs transfected with siRNA targeting Wnt2. As a result, cancer cell invasion and migration were significantly decreased in the CM from immortalized CAFs transfected with siRNA targeting Wnt2. Our findings indicated that Wnt2 protein released from CAFs enhances CRC cell invasion and migration. In conclusion, Wnt2 secreted by CAFs plays a key role in cancer progression and is a potential therapeutic target for CRC.
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