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Mol. Biol. Cell 22 (21): 3962-3970

Copyright © 2011 by The American Society for Cell Biology.


Cell Biology of Disease

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

Thomas W. Marshalla, Isaac E. Lloyda, Jean Marie Delalandea,*, Inke Näthkeb, and Jody Rosenblatta,{dagger}

aDepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112 bCell and Developmental Biology, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom

Received for publication May 31, 2011. Revision received August 24, 2011. Accepted for publication August 31, 2011.

Monitoring Editor: Alpha Yap

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.


This article was published online ahead of print in MBoC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E11-05-0469) on September 7, 2011.

*Present address: Institute of Child Health, University College London, London WC1N 1EH, United Kingdom.

{dagger}Address correspondence to: Jody Rosenblatt (jody.rosenblatt{at}hci.utah.edu).

Abbreviations: APC, adenomatous polyposis coli • HBE, human bronchial epithelial cells, 16HBE14 • shNS, nonspecific short hairpin RNA


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