PUBLICATION
The tumor suppressor adenomatous polyposis coli controls the direction a cell extrudes from an epithelium
- Authors
- Marshall, T.W., Lloyd, I.E., Delalande, J.M., Näthke, I., and Rosenblatt, J.
- ID
- ZDB-PUB-110914-14
- Date
- 2011
- Source
- Molecular biology of the cell 22(21): 3962-70 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Actins/metabolism
- Adenomatous Polyposis Coli Protein/genetics
- Adenomatous Polyposis Coli Protein/metabolism*
- Animals
- Cell Death
- Cell Line
- Epidermis/cytology
- Epidermis/physiology
- Epithelial Cells/physiology*
- Gene Knockdown Techniques
- Humans
- Microscopy, Confocal
- Microtubules/metabolism
- Oncogene Proteins/metabolism
- Peptide Fragments/metabolism
- Protein Structure, Tertiary
- Protein Transport
- RNA Interference
- Recombinant Proteins/metabolism
- Respiratory Mucosa/cytology*
- Respiratory Mucosa/physiology
- Single-Cell Analysis
- Tubulin/metabolism
- Zebrafish
- PubMed
- 21900494 Full text @ Mol. Biol. Cell
Citation
Marshall, T.W., Lloyd, I.E., Delalande, J.M., Näthke, I., and Rosenblatt, J. (2011) The tumor suppressor adenomatous polyposis coli controls the direction a cell extrudes from an epithelium. Molecular biology of the cell. 22(21):3962-70.
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 (Slattum et al, 2007). 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 common in colon and breast cancer may promote basal extrusion of tumor cells, which could enable their exit and subsequent migration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping