The tumor suppressor adenomatous polyposis coli controls the direction in which a cell extrudes from an epithelium

Thomas W. Marshall, Isaac E. Lloyd, Jean Marie Delalande, Inke Nathke, Jody Rosenblatt

    Research output: Contribution to journalArticle

    49 Citations (Scopus)

    Abstract

    Despite high rates of cell death, epithelia maintain intact barriers by squeezing dying cells out using a process termed cell extrusion. Cells can extrude apically into the lumen or basally into the tissue the epithelium encases, depending on whether actin and myosin contract at the cell base or apex, respectively. We previously found that microtubules in cells surrounding a dying cell target p115 RhoGEF to the actin cortex to control where contraction occurs. However, what controls microtubule targeting to the cortex and whether the dying cell also controls the extrusion direction were unclear. Here we find that the tumor suppressor adenomatous polyposis coli (APC) controls microtubule targeting to the cell base to drive apical extrusion. Whereas wild-type cells preferentially extrude apically, cells lacking APC or expressing an oncogenic APC mutation extrude predominantly basally in cultured monolayers and zebrafish epidermis. Thus APC is essential for driving extrusion apically. Surprisingly, although APC controls microtubule reorientation and attachment to the actin cortex in cells surrounding the dying cell, it does so by controlling actin and microtubules within the dying cell. APC disruptions that are common in colon and breast cancer may promote basal extrusion of tumor cells, which could enable their exit and subsequent migration.

    Original languageEnglish
    Pages (from-to)3962-3970
    Number of pages9
    JournalMolecular Biology of the Cell
    Volume22
    Issue number21
    Early online date7 Sep 2011
    DOIs
    Publication statusPublished - 1 Nov 2011

    Keywords

    • Microtubule stability
    • Protein
    • APC
    • Actin
    • Extrusion
    • Apoptosis
    • Migration
    • Pathway
    • Complex
    • Binding

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