Cited by 108Wnt/β-catenin signaling in development and cancerGenetic factors in colorectal cancerColorectal Cancer Treatments and Studies

Subcellular distribution of Wnt pathway proteins in normal and neoplastic colon

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Anderson, Christine B., Neufeld, Kristi L., White, Raymond L.·2002·Proceedings of the National Academy of Sciences

Abstract

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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Crossref · 10.1073/pnas.122235399

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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]”

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Authors
Anderson, C. B., Neufeld, K. L., & White, R. L.
Affiliations
University of Utah (US)
Venue
Proceedings of the National Academy of Sciences
Published
2002-06-18
Volume
99
Issue
13
Pages
8683-8688
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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