Cell and tissue polarity in the intestinal tract during tumourigenesis: Cells still know the right way up, but tissue organization is lost

Aliya Fatehullah, Paul L. Appleton, Inke S. Nathke

    Research output: Contribution to journalArticle

    33 Citations (Scopus)

    Abstract

    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.
    Original languageEnglish
    Article number20130014
    JournalPhilosophical Transactions of the Royal Society B - Biological Sciences
    Volume368
    Issue number1629
    DOIs
    Publication statusPublished - 5 Nov 2013

    Keywords

    • Adenomatous polyposis coli
    • POLARITY
    • Adhesion
    • Migration
    • tissue organization
    • organoid culture

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