DOCK7 is a critical regulator of the RAGE-Cdc42 signaling axis that induces formation of dendritic pseudopodia in human cancer cells

Yamamoto,Ken-Ichi; Murata,Hitoshi; Putranto,Endy  Widya; Kataoka,Ken; Motoyama,Akira; Hibino,Toshihiko; Inoue,Yusuke; Sakaguchi,Masakiyo; Huh,Nam-Ho

doi:10.3892/or.2012.2191

DOCK7 is a critical regulator of the RAGE-Cdc42 signaling axis that induces formation of dendritic pseudopodia in human cancer cells

Authors:
- Ken-Ichi Yamamoto
- Hitoshi Murata
- Endy Widya Putranto
- Ken Kataoka
- Akira Motoyama
- Toshihiko Hibino
- Yusuke Inoue
- Masakiyo Sakaguchi
- Nam-Ho Huh
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Affiliations: Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama 700-8558, Japan, Department of Life Science, Faculty of Science, Okayama University of Science, Kita-ku, Okayama 700-0005, Japan, Shiseido Research Center, Kanazawa-ku, Yokohama 236-8643, Japan, Department of Chemistry and Chemical Biology, Graduate School of Engineering, Gunma University, Kiryu, Gunma 376-8515, Japan
Published online on: December 17, 2012 https://doi.org/10.3892/or.2012.2191
Pages: 1073-1079

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Abstract

Cellular migration is a fundamental process linked to cancer metastasis. Growing evidence indicates that the receptor for advanced glycation end products (RAGE) plays a pivotal role in this process. With regard to downstream signal transducers of RAGE, diaphanous-1 and activated small guanine nucleotide triphosphatases, Rac1 and Cdc42, have been identified. To obtain precise insight into the direct downstream signaling mechanism of RAGE, we screened for proteins interacting with the cytoplasmic domain of RAGE employing an immunoprecipitation-liquid chromatography coupled with an electrospray tandem mass spectrometry system. In the present study, we found that the cytoplasmic domain of RAGE interacted with an atypical DOCK180-related guanine nucleotide exchange factor, dedicator of cytokinesis protein 7 (DOCK7). DOCK7 bound to the RAGE cytoplasmic domain and transduced a signal to Cdc42, resulting in the formation of abundant highly branched filopodia-like protrusions, dendritic pseudopodia. Blocking of the function of DOCK7 greatly abrogated the formation of dendritic pseudopodia and suppressed cellular migration. These results indicate that DOCK7 functions as an essential and downstream regulator of RAGE-mediated cellular migration through the formation of dendritic pseudopodia.

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