A JAM-A–tetraspanin–αvβ5 integrin complex regulates contact inhibition of locomotion
2022 | journal article
Jump to: Cite & Linked | Documents & Media | Details | Version history
Cite this publication
A JAM-A–tetraspanin–αvβ5 integrin complex regulates contact inhibition of locomotion
Kummer, D.; Steinbacher, T.; Thölmann, S.; Schwietzer, M. F.; Hartmann, C.; Horenkamp, S. & Demuth, S. et al. (2022)
The Journal of Cell Biology, 221(4). DOI: https://doi.org/10.1083/jcb.202105147
Documents & Media
Details
- Authors
- Kummer, Daniel; Steinbacher, Tim; Thölmann, Sonja; Schwietzer, Mariel Flavia; Hartmann, Christian; Horenkamp, Simone; Demuth, Sabrina; Peddibhotla, Swetha S.D.; Brinkmann, Frauke; Kemper, Björn; Schnekenburger, Jürgen; Brandt, Matthias; Betz, Timo ; Liashkovich, Ivan; Kouzel, Ivan U.; Shahin, Victor; Corvaia, Nathalie; Rottner, Klemens; Tarbashevich, Katsiaryna; Raz, Erez; Greune, Lilo; Schmidt, M. Alexander; Gerke, Volker; Ebnet, Klaus
- Abstract
- 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.
- Issue Date
- 2022
- Journal
- The Journal of Cell Biology
- ISSN
- 0021-9525