A JAM-A-tetraspanin-αvβ5 integrin complex regulates contact inhibition of locomotion.
|
| 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.
|
|---|---|
| Authors | 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 |
| Journal | The Journal of cell biology (J Cell Biol) Vol. 221 Issue 4 (04 04 2022) ISSN: 1540-8140 [Electronic] United States |
| PMID | 35293964 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | © 2022 Kummer et al. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!