Contact inhibition of locomotion (CIL) is a process that regulates cell motility upon collision with other cells. Improper regulation of CIL has been implicated in cancer cell dissemination. Here, we identify the cell adhesion molecule JAM-A as a central regulator of CIL in tumor cells. JAM-A is part of a multimolecular signaling complex in which tetraspanins CD9 and CD81 link JAM-A to αvβ5 integrin. JAM-A binds Csk and inhibits the activity of αvβ5 integrin-associated Src. Loss of JAM-A results in increased activities of downstream effectors of Src, including Erk1/2, Abi1, and paxillin, as well as increased activity of Rac1 at cell–cell contact sites. As a consequence, JAM-A-depleted cells show increased motility, have a higher cell–matrix turnover, and fail to halt migration when colliding with other cells. We also find that proper regulation of CIL depends on αvβ5 integrin engagement. Our findings identify a molecular mechanism that regulates CIL in tumor cells and have implications on tumor cell dissemination.
Skip Nav Destination
Article navigation
4 April 2022
Article|
March 16 2022
A JAM-A–tetraspanin–αvβ5 integrin complex regulates contact inhibition of locomotion
Daniel Kummer,
1
Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Münster, Germany
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
3
Interdisciplinary Clinical Research Center (IZKF), University of Münster, Münster, Germany
Search for other works by this author on:
Tim Steinbacher
,
1
Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Münster, Germany
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
Search for other works by this author on:
Sonja Thölmann
,
1
Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Münster, Germany
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
Search for other works by this author on:
Mariel Flavia Schwietzer,
Mariel Flavia Schwietzer
1
Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Münster, Germany
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
Search for other works by this author on:
Christian Hartmann
,
Christian Hartmann
1
Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Münster, Germany
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
Search for other works by this author on:
Simone Horenkamp
,
Simone Horenkamp
1
Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Münster, Germany
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
Search for other works by this author on:
Sabrina Demuth,
Sabrina Demuth
1
Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Münster, Germany
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
Search for other works by this author on:
Swetha S.D. Peddibhotla,
Swetha S.D. Peddibhotla
1
Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Münster, Germany
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
Search for other works by this author on:
Frauke Brinkmann,
Frauke Brinkmann
1
Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Münster, Germany
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
Search for other works by this author on:
Björn Kemper,
Björn Kemper
4
Biomedical Technology Center, Medical Faculty, University of Münster, Münster, Germany
Search for other works by this author on:
Jürgen Schnekenburger
,
Jürgen Schnekenburger
4
Biomedical Technology Center, Medical Faculty, University of Münster, Münster, Germany
Search for other works by this author on:
Matthias Brandt
,
Matthias Brandt
5
Institute-associated Research Group “Mechanics of Cellular Systems”, Institute of Cell Biology, ZMBE, University of Münster, Münster, Germany
Search for other works by this author on:
Timo Betz
,
Timo Betz
5
Institute-associated Research Group “Mechanics of Cellular Systems”, Institute of Cell Biology, ZMBE, University of Münster, Münster, Germany
Search for other works by this author on:
Ivan Liashkovich
,
Ivan Liashkovich
6
Institute of Physiology II, University of Münster, Münster, Germany
Search for other works by this author on:
Ivan U. Kouzel,
Ivan U. Kouzel
7
Sars International Centre for Marine Molecular Biology University of Bergen Thormøhlensgt, Bergen, Norway
Search for other works by this author on:
Victor Shahin,
Victor Shahin
6
Institute of Physiology II, University of Münster, Münster, Germany
Search for other works by this author on:
Nathalie Corvaia,
Nathalie Corvaia
8
Centre d’Immunologie Pierre Fabre (CIPF), Saint-Julien-en-Genevois, France
Search for other works by this author on:
Klemens Rottner
,
Klemens Rottner
9
Divison of Molecular Cell Biology, Zoological Institute, Technical University Braunschweig, Braunschweig, Germany
10
Molecular Cell Biology Group, Department of Cell Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany
Search for other works by this author on:
Katsiaryna Tarbashevich,
Katsiaryna Tarbashevich
11
Institute of Cell Biology, ZMBE, University of Münster, Münster, Germany
Search for other works by this author on:
Erez Raz
,
Erez Raz
11
Institute of Cell Biology, ZMBE, University of Münster, Münster, Germany
12
Cells-in-Motion Cluster of Excellence (EXC 1003—CiM), University of Münster, 48419 Münster, Germany
Search for other works by this author on:
Lilo Greune,
Lilo Greune
13
Institute of Infectiology, ZMBE, University of Münster, Münster, Germany
Search for other works by this author on:
M. Alexander Schmidt
,
M. Alexander Schmidt
13
Institute of Infectiology, ZMBE, University of Münster, Münster, Germany
Search for other works by this author on:
Volker Gerke
,
Volker Gerke
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
12
Cells-in-Motion Cluster of Excellence (EXC 1003—CiM), University of Münster, 48419 Münster, Germany
Search for other works by this author on:
Klaus Ebnet
Klaus Ebnet
1
Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Münster, Germany
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
3
Interdisciplinary Clinical Research Center (IZKF), University of Münster, Münster, Germany
12
Cells-in-Motion Cluster of Excellence (EXC 1003—CiM), University of Münster, 48419 Münster, Germany
Search for other works by this author on:
1
Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Münster, Germany
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
3
Interdisciplinary Clinical Research Center (IZKF), University of Münster, Münster, Germany
1
Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Münster, Germany
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
1
Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Münster, Germany
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
Mariel Flavia Schwietzer
1
Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Münster, Germany
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
Christian Hartmann
1
Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Münster, Germany
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
Simone Horenkamp
1
Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Münster, Germany
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
Sabrina Demuth
1
Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Münster, Germany
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
Swetha S.D. Peddibhotla
1
Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Münster, Germany
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
Frauke Brinkmann
1
Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Münster, Germany
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
Björn Kemper
4
Biomedical Technology Center, Medical Faculty, University of Münster, Münster, Germany
Jürgen Schnekenburger
4
Biomedical Technology Center, Medical Faculty, University of Münster, Münster, Germany
Matthias Brandt
5
Institute-associated Research Group “Mechanics of Cellular Systems”, Institute of Cell Biology, ZMBE, University of Münster, Münster, Germany
Timo Betz
5
Institute-associated Research Group “Mechanics of Cellular Systems”, Institute of Cell Biology, ZMBE, University of Münster, Münster, Germany
Ivan Liashkovich
6
Institute of Physiology II, University of Münster, Münster, Germany
Ivan U. Kouzel
7
Sars International Centre for Marine Molecular Biology University of Bergen Thormøhlensgt, Bergen, Norway
Victor Shahin
6
Institute of Physiology II, University of Münster, Münster, Germany
Nathalie Corvaia
8
Centre d’Immunologie Pierre Fabre (CIPF), Saint-Julien-en-Genevois, France
Klemens Rottner
9
Divison of Molecular Cell Biology, Zoological Institute, Technical University Braunschweig, Braunschweig, Germany
10
Molecular Cell Biology Group, Department of Cell Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany
Katsiaryna Tarbashevich
11
Institute of Cell Biology, ZMBE, University of Münster, Münster, Germany
11
Institute of Cell Biology, ZMBE, University of Münster, Münster, Germany
12
Cells-in-Motion Cluster of Excellence (EXC 1003—CiM), University of Münster, 48419 Münster, Germany
Lilo Greune
13
Institute of Infectiology, ZMBE, University of Münster, Münster, Germany
M. Alexander Schmidt
13
Institute of Infectiology, ZMBE, University of Münster, Münster, Germany
Volker Gerke
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
12
Cells-in-Motion Cluster of Excellence (EXC 1003—CiM), University of Münster, 48419 Münster, Germany
Klaus Ebnet
1
Institute-associated Research Group “Cell Adhesion and Cell Polarity”, Münster, Germany
2
Institute of Medical Biochemistry, ZMBE, University of Münster, Münster, Germany
3
Interdisciplinary Clinical Research Center (IZKF), University of Münster, Münster, Germany
12
Cells-in-Motion Cluster of Excellence (EXC 1003—CiM), University of Münster, 48419 Münster, Germany
Correspondence to Klaus Ebnet: ebnetk@uni-muenster.de
*
Daniel Kummer, Tim Steinbacher, and Sonja Thölmann contributed equally to this paper.
Received:
May 25 2021
Revision Received:
December 16 2021
Accepted:
January 21 2022
Online Issn: 1540-8140
Print Issn: 0021-9525
Funding
Funder(s):
Deutsche Forschungsgemeinschaft
- Award Id(s): EB 160/7-1,EXC1003-CiM FF-2016-1,SFB1348/A04
Funder(s):
University of Münster
- Award Id(s): IZKF Eb2/020/14,MedK 17-0075
© 2022 Kummer et al.
2022
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2022) 221 (4): e202105147.
Article history
Received:
May 25 2021
Revision Received:
December 16 2021
Accepted:
January 21 2022
Citation
Daniel Kummer, Tim Steinbacher, Sonja Thölmann, Mariel Flavia Schwietzer, Christian Hartmann, Simone Horenkamp, Sabrina Demuth, Swetha S.D. Peddibhotla, Frauke Brinkmann, Björn Kemper, Jürgen Schnekenburger, Matthias Brandt, Timo Betz, Ivan Liashkovich, Ivan U. Kouzel, Victor Shahin, Nathalie Corvaia, Klemens Rottner, Katsiaryna Tarbashevich, Erez Raz, Lilo Greune, M. Alexander Schmidt, Volker Gerke, Klaus Ebnet; A JAM-A–tetraspanin–αvβ5 integrin complex regulates contact inhibition of locomotion. J Cell Biol 4 April 2022; 221 (4): e202105147. doi: https://doi.org/10.1083/jcb.202105147
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Sign in via your Institution
Sign in via your Institution
764
Views
0
Citations
Suggested Content
Advertisement
Advertisement