Loss of contact inhibition of locomotion in the absence of JAM-A promotes entotic cell engulfment

Mariel F. Schwietzer; Sonja Thölmann; Daniel Kummer; Anne Kaschler; Lilo Greune; Eva-Maria Thüring; M. Alexander Schmidt; Volker Gerke; Klaus Ebnet

iScience (Oct 2022)

Loss of contact inhibition of locomotion in the absence of JAM-A promotes entotic cell engulfment

Mariel F. Schwietzer,
Sonja Thölmann,
Daniel Kummer,
Anne Kaschler,
Lilo Greune,
Eva-Maria Thüring,
M. Alexander Schmidt,
Volker Gerke,
Klaus Ebnet

Affiliations

Mariel F. Schwietzer: Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Institute of Medical Biochemistry, ZMBE, University of Münster, Von-Esmarch-Str. 56, 48149 Münster, Germany
Sonja Thölmann: Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Institute of Medical Biochemistry, ZMBE, University of Münster, Von-Esmarch-Str. 56, 48149 Münster, Germany
Daniel Kummer: Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Institute of Medical Biochemistry, ZMBE, University of Münster, Von-Esmarch-Str. 56, 48149 Münster, Germany
Anne Kaschler: Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Institute of Medical Biochemistry, ZMBE, University of Münster, Von-Esmarch-Str. 56, 48149 Münster, Germany
Lilo Greune: Institute of Infectiology, ZMBE, University of Münster, 48149 Münster, Germany
Eva-Maria Thüring: Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Institute of Medical Biochemistry, ZMBE, University of Münster, Von-Esmarch-Str. 56, 48149 Münster, Germany
M. Alexander Schmidt: Institute of Infectiology, ZMBE, University of Münster, 48149 Münster, Germany
Volker Gerke: Institute of Medical Biochemistry, ZMBE, University of Münster, 48149 Münster, Germany
Klaus Ebnet: Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Institute of Medical Biochemistry, ZMBE, University of Münster, Von-Esmarch-Str. 56, 48149 Münster, Germany; Interdisciplinary Clinical Research Center (IZKF), University of Münster, 48149 Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC 1003 - CiM), University of Münster, 48419 Münster, Germany; Corresponding author

Journal volume & issue: Vol. 25, no. 10
p. 105144

Abstract

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Summary: Entosis is a cell competition process during which tumor cells engulf other tumor cells. It is initiated by metabolic stress or by loss of matrix adhesion, and it provides the winning cell with resources derived from the internalized cell. Using micropatterns as substrates for single cell migration, we find that the depletion of the cell adhesion receptor JAM-A strongly increases the rate of entosis in matrix-adherent cells. The activity of JAM-A in suppressing entosis depends on phosphorylation at Tyr280, which is a binding site for C-terminal Src kinase, and which we have previously found to regulate tumor cell motility and contact inhibition of locomotion (CIL). Loss of JAM-A triggers entosis in matrix-adherent cells but not matrix-deprived cells. Our findings strongly suggest that the increased motility and the perturbed CIL response after the depletion of JAM-A promote entotic cell engulfment, and they link a dysregulation of CIL to entosis in breast cancer cells.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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