ArticleJournal of experimental & clinical cancer research : CR2020
WNT4 secreted by tumor tissues promotes tumor progression in colorectal cancer by activation of the Wnt/β-catenin signalling pathway.
Article in Journal of experimental & clinical cancer research : CR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 69 citations in OpenAlex.
- Spatial Transcriptomics Reveals Location-Specific Tumor Cell Subtypes and Signaling within Multifocal Small Intestinal Neuroendocrine Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Reciprocal inhibition of Wnt signaling pathways pattern the interconnection of epithelial tubules in the regenerating zebrafish kidney.Development (Cambridge, England) · 2026Article
- PLK1 stabilizes β-catenin to drive colorectal carcinogenesis through NFKB2-mediated transcriptional activation of USP2a and site-specific phosphorylation.Theranostics · 2026Article
- Cancer-Associated Fibroblasts in Gastrointestinal Cancer Metastasis: Mechanisms and Emerging Therapeutic Strategies.Drug design, development and therapy · 2026Review
- Targeted protein degradation of Wnt/β-catenin signaling pathway: an effective strategy for cancer therapy.Journal of translational medicine · 2025Review
- Intercellular signaling reinforces single-cell level phenotypic transitions and facilitates robust re-equilibrium of heterogeneous cancer cell populations.Cell communication and signaling : CCS · 2025Article
- The Significance of the Wnt/β-Catenin Pathway and Related Proteins in Gastrointestinal Malignancies.International journal of molecular sciences · 2025Review
- Evolutionary conservation and cancer implications of the WNT signaling pathway.Medical oncology (Northwood, London, England) · 2025Review
- Expression Pattern of AIFM3, VGLL4, and WNT4 in Patients with Different Stages of Colorectal Cancer.Cancers · 2025Article
- Unleashing Wnts: Wnt Ligands Fuel Cancer Spread.Journal of cancer biology · 2025Article
- Single-cell landscape of the intrahepatic ecosystem in alcohol-related liver disease.Clinical and translational medicine · 2025Article
- Molecular Mechanisms of Synergistic Effect of PRIMA-1Cancer medicine · 2025Article
- WYC-209 inhibited GC malignant progression by down-regulating WNT4 through RARα.Cancer biology & therapy · 2024Article
- Interplay between JAK/STAT pathway and non-coding RNAs in different cancers.Non-coding RNA research · 2024Review
- Emerging roles and biomarker potential of WNT6 in human cancers.Cell communication and signaling : CCS · 2024Review
- Development and Validation of an AI-Driven System for Automatic Literature Analysis and Molecular Regulatory Network Construction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Elevated BEAN1 expression correlates with poor prognosis, immune evasion, and chemotherapy resistance in rectal adenocarcinoma.Discover oncology · 2024Article
- NR3C2 affects the proliferation and invasiveness of colon cancer cells through the Wnt/β-Catenin signaling pathway.Journal of cancer research and clinical oncology · 2024Article
- Article
- The ubiquitin-like protein FAT10 in hepatocellular carcinoma cells limits the efficacy of anti-VEGF therapy.Journal of advanced research · 2024Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundWingless and Int-related protein (Wnt) ligands are aberrantly expressed in patients with colorectal cancer (CRC). However, the aberrant level of Wnt ligands in serum have not been explored. Here, we aimed to identify the levels of WNT4 in serum and explored its oncogenic role in CRC.
methodsThe Oncomine database was used to analyze the relationship between WNT4 and the prognosis of CRC. ELISA was performed to measure WNT4 levels in serum and conditioned medium from fresh CRC tissues and adjacent normal tissues. Western blot and immunohistochemistry were carried out to measure the expression of WNT4 in human CRC tissues and adjacent normal tissues. The migration and invasion of CRC cells were determined by trans-well assay, and the effects of WNT4 on CRC invasion and metastasis in vivo were verified by tumor xenograft in nude mice. Cancer-associated fibroblasts (CAFs) and angiogenesis in subcutaneous nodules were detected by immunofluorescence (IF). In addition, the suspended spheres formation and tube formation assay were performed to explore the effects of WNT4 on CAFs and angiogenesis respectively.
resultsWNT4 was significantly upregulated in serum of CRC patients, and CRC tissues were identified as an important source of elevated WNT4 levels in CRC patients. Interestingly, elevated levels of WNT4 in serum were downregulated after tumor resection. Furthermore, we found that WNT4 contributed to epithelial-to-mesenchymal transition (EMT) and activated fibroblasts by activating the WNT4/β-catenin pathway in vitro and in vivo. Moreover, angiogenesis was induced via the WNT4/β-catenin/Ang2 pathway. Those effects could be reversed by ICG-001, a β-catenin/TCF inhibitor.
conclusionOur findings indicated that serum levels of WNT4 may be a potential biomarker for CRC. WNT4 secreted by colorectal cancer tissues promote the progression of CRC by inducing EMT, activate fibroblasts and promote angiogenesis through the canonical Wnt/β-catenin signalling pathway.
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