AJAM-A–tetraspanin–αvβ5 integrin complex regulates contact inhibition of locomotion
| Autor: | 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 |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | e202105147 Journal of Cell Biology |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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