ArticleBritish journal of cancer2015
The BMP pathway either enhances or inhibits the Wnt pathway depending on the SMAD4 and p53 status in CRC.
Article in British journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 78 citations in OpenAlex.
- Article
- PLK1 stabilizes β-catenin to drive colorectal carcinogenesis through NFKB2-mediated transcriptional activation of USP2a and site-specific phosphorylation.Theranostics · 2026Article
- Inhibition of Wnt signaling in primary human hepatocytes promotes Plasmodium falciparum liver stage development.PLoS pathogens · 2025Article
- Gut microbes and their metabolites in relation to the classic tumor suppressor gene P53: a novel narrative.NPJ biofilms and microbiomes · 2025Review
- BMP signalling in colorectal cancer: losing the yin to WNTs yang.The Journal of pathology · 2025Review
- Article
- GSK3β Inhibitors Inhibit TGFβ Signaling in the Human Trabecular Meshwork.Investigative ophthalmology & visual science · 2024Article
- TGF-β Modulated Pathways in Colorectal Cancer: New Potential Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- BMP Stimulation Differentially Affects Phosphorylation and Protein Stability of β-Catenin in Breast Cancer Cell Lines.International journal of molecular sciences · 2024Article
- Significant Genes Associated with Mortality and Disease Progression in Grade II and III Glioma.Biomedicines · 2024Article
- The molecular mechanisms underlying the regeneration process in the earthworm, Perionyx excavatus exhibit indications of apoptosis-induced compensatory proliferation (AICP).In vitro cellular & developmental biology. Animal · 2024Article
- Expression Analysis of Early Metastatic Seeding of Colorectal Cancer.Annals of surgical oncology · 2024Article
- Metabolic Heterogeneity of Tumor Cells and its Impact on Colon Cancer Metastasis: Insights from Single-Cell and Bulk Transcriptome Analyses.Journal of Cancer · 2024Article
- In Vitro Organoid-Based Assays Reveal SMAD4 Tumor-Suppressive Mechanisms for Serrated Colorectal Cancer Invasion.Cancers · 2023Article
- AnMaterials today. Bio · 2023Article
- Inhibition of the bone morphogenetic protein pathway suppresses tumor growth through downregulation of epidermal growth factor receptor in MEK/ERK-dependent colorectal cancer.Cancer science · 2023Article
- Escin Activates Canonical Wnt/β-Catenin Signaling Pathway by Facilitating the Proteasomal Degradation of Glycogen Synthase Kinase-3β in Cultured Human Dermal Papilla Cells.Current issues in molecular biology · 2023Article
- Biallelic FBXW7 knockout induces AKAP8-mediated DNA damage in neighbouring wildtype cells.Cell death discovery · 2023Article
- Blocking the Wnt/β‑catenin signaling pathway to treat colorectal cancer: Strategies to improve current therapies (Review).International journal of oncology · 2023Review
- Multiomics of Colorectal Cancer Organoids Reveals Putative Mediators of Cancer Progression Resulting from SMAD4 Inactivation.Journal of proteome research · 2023Article
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Authors and funding
21 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundConstitutive Wnt activation is essential for colorectal cancer (CRC) initiation but also underlies the cancer stem cell phenotype, metastasis and chemosensitivity. Importantly Wnt activity is still modulated as evidenced by higher Wnt activity at the invasive front of clonal tumours termed the β-catenin paradox. SMAD4 and p53 mutation status and the bone morphogenetic protein (BMP) pathway are known to affect Wnt activity. The combination of SMAD4 loss, p53 mutations and BMP signalling may integrate to influence Wnt signalling and explain the β-catenin paradox.
methodsWe analysed the expression patterns of SMAD4, p53 and β-catenin at the invasive front of CRCs using immunohistochemistry. We activated BMP signalling in CRC cells in vitro and measured BMP/Wnt activity using luciferase reporters. MTT assays were performed to study the effect of BMP signalling on CRC chemosensitivity.
resultsEighty-four percent of CRCs with high nuclear β-catenin staining are SMAD4 negative and/or p53 aberrant. BMP signalling inhibits Wnt signalling in CRC only when p53 and SMAD4 are unaffected. In the absence of SMAD4, BMP signalling activates Wnt signalling. When p53 is lost or mutated, BMP signalling no longer influences Wnt signalling. The cytotoxic effects of 5-FU are influenced in a similar manner.
conclusionsThe BMP signalling pathway differentially modulates Wnt signalling dependent on the SMAD4 and p53 status. The use of BMPs in cancer therapy, as has been proposed by previous studies, should be targeted to individual cancers based on the mutational status of p53 and SMAD4.
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