Cell and tissue polarity in the intestinal tract during tumourigenesis: cells still know the right way up, but tissue organization is lost
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Cell and tissue polarity are tightly coupled and are vital for normal tissue homeostasis. Changes in cellular and tissue organization are common to even early stages of disease, particularly cancer. The digestive tract is the site of the second most common cause of cancer deaths in the developed world. Tumours in this tissue arise in an epithelium that has a number of axes of cell and tissue polarity. Changes in cell and tissue polarity in response to genetic changes that are known to underpin disease progression provide clues about the link between molecular-, cellular- and tissue-based mechanisms that accompany cancer. Mutations in adenomatous polyposis coli (APC) are common to most colorectal cancers in humans and are sufficient to cause tumours in mouse intestine. Tissue organoids mimic many features of whole tissue and permit identifying changes at different times after inactivation of APC. Using gut organoids, we show that tissue polarity is lost very early during cancer progression, whereas cell polarity, at least apical–basal polarity, is maintained and changes only at later stages. These observations reflect the situation in tumours and validate tissue organoids as a useful system to investigate the relationship between cell polarity and tissue organization.
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β4 integrin expressed by intestinal organoids is distributed only at the basal surface, while β1 integrin is required for proper apical-basal polarization.
“β4 integrin expressed by intestinal organoids is distributed only at the basal surface94, while β1 integrin is required for proper apical-basal polarization95–97.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [94]
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- Authors
- Fatehullah, A., Appleton, P. L., & Näthke, I. S.
- Affiliations
- University of Dundee (GB)
- Corresponding author
- Näthke, Inke S.
- Venue
- Philosophical Transactions of the Royal Society B: Biological Sciences
- Publisher
- The Royal Society
- Published
- 2013-11-05
- Volume
- 368
- Issue
- 1629
- Pages
- 20130014
- ISSN
- 0962-8436 (ISSN-L)
- 1471-2970
- PMC
- PMC3785964
- OpenAlex
- W2156939613
- Cited by
- 65
- References
- 49
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 9 · 2018: 7 · 2017: 11 · 2016: 6 · 2015: 3 · 2013: 2
- FWCI
- 1.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Philosophical Transactions of the Royal Society B Biological Sciences (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- Funders
- Cancer Research UK (A11243, 11243)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- cell polarity, tissue polarity, colorectal cancer, apical-basal polarity, adenomatous polyposis coli, APC mutation, tissue organization, tumor progression, intestinal epithelium
- MeSH terms
- Animals, Cell Adhesion, Fluorescent Antibody Technique, Image Processing, Computer-Assisted, Mice, Inbred C57BL, Organoids, Adenomatous Polyposis Coli, Cell Polarity, Gastrointestinal Tract, Mice, Carcinogenesis
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