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
  • View Affiliations

  • 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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March 2013
Volume 29 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Yamamoto K, Murata H, Putranto EW, Kataoka K, Motoyama A, Hibino T, Inoue Y, Sakaguchi M and Huh N: DOCK7 is a critical regulator of the RAGE-Cdc42 signaling axis that induces formation of dendritic pseudopodia in human cancer cells. Oncol Rep 29: 1073-1079, 2013
APA
Yamamoto, K., Murata, H., Putranto, E.W., Kataoka, K., Motoyama, A., Hibino, T. ... Huh, N. (2013). DOCK7 is a critical regulator of the RAGE-Cdc42 signaling axis that induces formation of dendritic pseudopodia in human cancer cells. Oncology Reports, 29, 1073-1079. https://doi.org/10.3892/or.2012.2191
MLA
Yamamoto, K., Murata, H., Putranto, E. W., Kataoka, K., Motoyama, A., Hibino, T., Inoue, Y., Sakaguchi, M., Huh, N."DOCK7 is a critical regulator of the RAGE-Cdc42 signaling axis that induces formation of dendritic pseudopodia in human cancer cells". Oncology Reports 29.3 (2013): 1073-1079.
Chicago
Yamamoto, K., Murata, H., Putranto, E. W., Kataoka, K., Motoyama, A., Hibino, T., Inoue, Y., Sakaguchi, M., Huh, N."DOCK7 is a critical regulator of the RAGE-Cdc42 signaling axis that induces formation of dendritic pseudopodia in human cancer cells". Oncology Reports 29, no. 3 (2013): 1073-1079. https://doi.org/10.3892/or.2012.2191