Observational studyThe American journal of pathology2018
c-Cbl Expression Correlates with Human Colorectal Cancer Survival and Its Wnt/β-Catenin Suppressor Function Is Regulated by Tyr371 Phosphorylation.
Observational study in The American journal of pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Genetic landscape of stage II melanoma identifies CBL as a new driver gene and prognostic biomarker.British journal of cancer · 2026Article
- New insights into the role of ubiquitination in angiogenesis (Review).International journal of molecular medicine · 2025Review
- Deep phosphotyrosine characterisation of primary murine T cells using broad spectrum optimisation of selective triggering.Proteomics · 2024Article
- Cbl and Cbl-b ubiquitin ligases are essential for intestinal epithelial stem cell maintenance.iScience · 2024Article
- The role of CBL family ubiquitin ligases in cancer progression and therapeutic strategies.Frontiers in pharmacology · 2024Review
- Effects of RNA methylation on Tumor angiogenesis and cancer progression.Molecular cancer · 2023Review
- Chalcone Derivative CX258 Suppresses Colorectal Cancer via Inhibiting the TOP2A/Wnt/β-Catenin Signaling.Cells · 2023Article
- CDK9 inhibitors downregulate DKK1 expression to suppress the metastatic potential of HCC cells.Genes & genomics · 2023Article
- Identification of BGN and THBS2 as metastasis-specific biomarkers and poor survival key regulators in human colon cancer by integrated analysis.Clinical and translational medicine · 2022Article
- SERPINA5 promotes tumour cell proliferation by modulating the PI3K/AKT/mTOR signalling pathway in gastric cancer.Journal of cellular and molecular medicine · 2022Article
- Pharmacologic Manipulation of Late SV40 Factor Suppresses Wnt Signaling and Inhibits Growth of Allogeneic and Syngeneic Colon Cancer Xenografts.The American journal of pathology · 2022Article
- Circular RNA circ_0068464 combined with microRNA-383 regulates Wnt/β-catenin pathway to promote the progression of colorectal cancer.Bioengineered · 2022Article
- The Role of Membrane-Associated E3 Ubiquitin Ligases in Cancer.Frontiers in pharmacology · 2022Review
- The role of CXCL10 in prognosis of patients with colon cancer and tumor microenvironment remodeling.Medicine · 2021Article
- A Novel N-Sulfonylamidine-Based Derivative Inhibits Proliferation, Migration, and Invasion in Human Colorectal Cancer Cells by Suppressing Wnt/β-Catenin Signaling Pathway.Pharmaceutics · 2021Article
- Comparison of SYK Signaling Networks Reveals the Potential Molecular Determinants of Its Tumor-Promoting and Suppressing Functions.Biomolecules · 2021Article
- Review
- Article
- Article
- 5-FU promotes stemness of colorectal cancer via p53-mediated WNT/β-catenin pathway activation.Nature communications · 2020Article
Corrections and comments
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
Abstract
The proto-oncogene β-catenin drives colorectal cancer (CRC) tumorigenesis. Casitas B-lineage lymphoma (c-Cbl) inhibits CRC tumor growth through targeting nuclear β-catenin by a poorly understood mechanism. In addition, the role of c-Cbl in human CRC remains largely underexplored. Using a novel quantitative histopathologic technique, we demonstrate that patients with high c-Cbl-expressing tumors had significantly better median survival (3.7 years) compared with low c-Cbl-expressing tumors (1.8 years; P = 0.0026) and were more than twice as likely to be alive at 3 years compared with low c-Cbl tumors (P = 0.0171). Our data further demonstrate that c-Cbl regulation of nuclear β-catenin requires phosphorylation of c-Cbl Tyr371 because its mutation compromises its ability to target β-catenin. The tyrosine 371 (Y371H) mutant interacted with but failed to ubiquitinate nuclear β-catenin. The nuclear localization of the c-Cbl-Y371H mutant contributed to its dominant negative effect on nuclear β-catenin. The biological importance of c-Cbl-Y371H was demonstrated in various systems, including a transgenic Wnt-8 zebrafish model. c-Cbl-Y371H mutant showed augmented Wnt/β-catenin signaling, increased Wnt target genes, angiogenesis, and CRC tumor growth. This study demonstrates a strong link between c-Cbl and overall survival of patients with CRC and provides new insights into a possible role of Tyr371 phosphorylation in Wnt/β-catenin regulation, which has important implications in tumor growth and angiogenesis in CRC.
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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.