Subcellular distribution of Wnt pathway proteins in normal and neoplastic colon
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Mutations in the APC tumor suppressor gene are present in approximately 85% of colorectal tumors and are thought to contribute early in the process of tumorigenesis. The truncated protein resulting from most APC mutations can lead to elevated beta-catenin levels in colon tumor cells. APC and associated proteins thus form a beta-catenin regulatory complex, with axin playing a key role. Although cell culture studies have revealed intriguing aspects of this complex, little characterization has been done in human colonocytes, the target tissue of colon carcinogenesis. The present study of intact human colon crypts, adenomatous polyps, and adenocarcinomas focuses on subcellular localization of some key elements of the complex: beta-catenin, APC, axin, and axin2. We examined endogenous protein localization within the framework of three-dimensional tissue architecture by using laser scanning confocal microscopy, and immunofluorescence staining of whole-mount fixed tissue from more than 50 patients. Expression patterns suggest that APC and axin colocalize in the nucleus and at lateral cell borders, and show that axin2 is limited to the nucleus. Altered nuclear expression of axin seen in colon polyps and carcinomas may be a consequence of the loss of full-length APC and the advent of nuclear beta-catenin. The observation of nuclear beta-catenin in fewer than half of carcinoma images and only rarely in polyps indicates that nuclear translocation of beta-catenin may not be an immediate…
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The accepted causal relationship between mutated APC, dysregulated Wnt signaling, proliferation and colorectal cancer development does not hold at least during the earliest stages of malignant transformation.
“improved diagnostic tools and better access to early lesions have found that this is not the case, at least during the earliest stages of malignant transformation [6–8]”
From Modeling APC mutagenesis and familial adenomatous polyposis using human iPS cells (2018) · cites this paper as [6]
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- Authors
- Anderson, C. B., Neufeld, K. L., & White, R. L.
- Affiliations
- University of Utah (US)
- ORCID
- Neufeld, Kristi L.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2002-06-18
- Volume
- 99
- Issue
- 13
- Pages
- 8683-8688
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC124359
- OpenAlex
- W2058194940
- Cited by
- 108
- References
- 34
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 2 · 2016: 6 · 2015: 5 · 2014: 9 · 2013: 9 · 2012: 7
- FWCI
- 1.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Huntsman Cancer Institute
- National Institutes of Health (5p01ca073992-15)
- National Cancer Institute (P01‐CA073992, 5P01 CA73992-02)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- Wnt signaling, β-catenin, Axin, Axin2, subcellular protein localization, colonic crypts, adenomatous polyps, colon adenocarcinoma, colorectal carcinogenesis
- MeSH terms
- Animals, Cell Nucleus, Colon, Cytoskeletal Proteins, Humans, Microscopy, Fluorescence, Proteins, Proto-Oncogene Proteins, Repressor Proteins, Subcellular Fractions, Colorectal Neoplasms, Trans-Activators, Genes, APC, Adenomatous Polyps, Zebrafish Proteins, Wnt Proteins, beta Catenin, Mice, Axin Protein
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