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The tetraspanin CD9 modulates epidermal growth factor receptor signaling in cancer cells
Author(s) -
Murayama Yoko,
Shinomura Yasuhisa,
Oritani Kenji,
Miyagawa JunIchiro,
Yoshida Hitoshi,
Nishida Makoto,
Katsube Fumie,
Shiraga Masamichi,
Miyazaki Tamana,
Nakamoto Taisei,
Tsutsui Shusaku,
Tamura Shinji,
Higashiyama Shigeki,
Shimomura Iichirou,
Hayashi Norio
Publication year - 2008
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21384
Subject(s) - epidermal growth factor receptor , tetraspanin , microbiology and biotechnology , autocrine signalling , cancer cell , cancer research , integrin , signal transduction , epidermal growth factor , cell growth , cd81 , cell , chinese hamster ovary cell , chemistry , biology , receptor , cancer , immunology , hepatitis c virus , biochemistry , genetics , virus
CD9 is a member of the tetraspanins, and has been shown to be involved in a variety of cellular activities such as migration, proliferation, and adhesion. In addition, it has been known that CD9 can associate with other proteins. Here we demonstrated the physical and functional association of CD9 with epidermal growth factor receptor (EGFR) on MKN‐28 cells. Double‐immunofluorescent staining and immunoprecipitation demonstrated the complex formation of CD9‐EGFR and CD9‐β 1 integrin, and that both complexes are colocalized on the cell surface especially at the cell–cell contact site. Anti‐CD9 monoclonal antibody ALB6 induced a dotted or patch‐like aggregation pattern of both CD9‐EGFR and CD9‐β 1 integrin. The internalization of EGFR after EGF‐stimulation was significantly enhanced by the treatment with ALB6. CD9 can associate with EGFR in hepatocellular carcinoma cells (HepG2/CD9) and Chinese hamster ovary cancer cells (CHO‐HER/CD9), which were transfected with pTJ/human EGFR/CD9. Furthermore expression of CD9 specifically attenuated EGFR signaling in CHO‐HER/CD9 cells through the down regulation of surface expression of EGFR. These results suggest that CD9 might have an important role that attenuates EGFR signaling. Therefore, CD9 not only associates EGFR but also a new regulator, which may affect EGF‐induced signaling in cancer cells. J. Cell. Physiol. 216: 135–143, 2008. © 2008 Wiley‐Liss, Inc.