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Caveolae Control Contractile Tension for Epithelia to Eliminate Tumor Cells.
- Source :
-
Developmental cell [Dev Cell] 2020 Jul 06; Vol. 54 (1), pp. 75-91.e7. Date of Electronic Publication: 2020 Jun 01. - Publication Year :
- 2020
-
Abstract
- Epithelia are active materials where mechanical tension governs morphogenesis and homeostasis. But how that tension is regulated remains incompletely understood. We now report that caveolae control epithelial tension and show that this is necessary for oncogene-transfected cells to be eliminated by apical extrusion. Depletion of caveolin-1 (CAV1) increased steady-state tensile stresses in epithelial monolayers. As a result, loss of CAV1 in the epithelial cells surrounding oncogene-expressing cells prevented their apical extrusion. Epithelial tension in CAV1-depleted monolayers was increased by cortical contractility at adherens junctions. This reflected a signaling pathway, where elevated levels of phosphoinositide-4,5-bisphosphate (PtdIns(4,5)P <subscript>2</subscript> ) recruited the formin, FMNL2, to promote F-actin bundling. Steady-state monolayer tension and oncogenic extrusion were restored to CAV1-depleted monolayers when tension was corrected by depleting FMNL2, blocking PtdIns(4,5)P <subscript>2</subscript> , or disabling the interaction between FMNL2 and PtdIns(4,5)P <subscript>2</subscript> . Thus, caveolae can regulate active mechanical tension for epithelial homeostasis by controlling lipid signaling to the actin cytoskeleton.<br />Competing Interests: Declaration of Interests The authors declare no competing interests.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Subjects :
- Actin Cytoskeleton metabolism
Animals
Caco-2 Cells
Caveolin 1 metabolism
Epithelial Cells ultrastructure
Formins metabolism
HEK293 Cells
Humans
Male
Mice
Oncogene Proteins genetics
Phosphatidylinositol 4,5-Diphosphate metabolism
Stress, Mechanical
Caveolae metabolism
Epithelial Cells metabolism
Oncogene Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1551
- Volume :
- 54
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Developmental cell
- Publication Type :
- Academic Journal
- Accession number :
- 32485139
- Full Text :
- https://doi.org/10.1016/j.devcel.2020.05.002