細胞運動の制御機構と蛋白分解酵素 Mechanism of cell migration and proteolysis

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Author(s)

    • 伊藤 和幸 Itoh Kazuyuki
    • 大阪成人セ・研・生物 Department of Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

Abstract

Cell migration is fundamental process implicated in physiological activities such as neurite extension and embryonic morphogenesis, and pathological activities including inflammation, wound healing and cancer invasion/metastasis. This process requires number of protein degrading events driven by several proteolytic enzymes. Among them, families of matrix metal proteinases (MMPs) were most deeply investigated, since it was thought to be a target for anti-cancer therapy. However, cancer therapeutics designed to target several MMPs have not proven to be effective for cancer progression under several clinical trials. This might be due to the fact that cancer cells modify their migration mode adjusted to the different conditions. Cancer cell motility involves integrin signaling, focal contact formation and actomyosin dependent contractility. Extracellular matrix (ECM) degrading enzymes, such as MMPs and cathepsins are frequently upregulated in tumor cells, facilitate migration in vitro, and dissemination and metastasis in vivo. In addition, the overexpression and/or activation of Rho family small GTPases (Rho, Rac) and downstream ROCK-MLCK pathways and LIMK pathways have been correlated with in vitro tumor cell migration and in vivo tumor progression and metastasis. However, due to its heterogeneity, tumor cells still can move in the 3D collagen even in the presence of number of protease inhibitor mixtures, by adapting the motile mode from path-generating to path-finding. In this symposium, I am going to focus on the recent developed concept of cancer cell migration and the involvement of proteases. <b>[J Physiol Sci. 2007;57 Suppl:S59]</b>

Cell migration is fundamental process implicated in physiological activities such as neurite extension and embryonic morphogenesis, and pathological activities including inflammation, wound healing and cancer invasion/metastasis. This process requires number of protein degrading events driven by several proteolytic enzymes. Among them, families of matrix metal proteinases (MMPs) were most deeply investigated, since it was thought to be a target for anti-cancer therapy. However, cancer therapeutics designed to target several MMPs have not proven to be effective for cancer progression under several clinical trials. This might be due to the fact that cancer cells modify their migration mode adjusted to the different conditions. Cancer cell motility involves integrin signaling, focal contact formation and actomyosin dependent contractility. Extracellular matrix (ECM) degrading enzymes, such as MMPs and cathepsins are frequently upregulated in tumor cells, facilitate migration in vitro, and dissemination and metastasis in vivo. In addition, the overexpression and/or activation of Rho family small GTPases (Rho, Rac) and downstream ROCK-MLCK pathways and LIMK pathways have been correlated with in vitro tumor cell migration and in vivo tumor progression and metastasis. However, due to its heterogeneity, tumor cells still can move in the 3D collagen even in the presence of number of protease inhibitor mixtures, by adapting the motile mode from path-generating to path-finding. In this symposium, I am going to focus on the recent developed concept of cancer cell migration and the involvement of proteases. <b>[J Physiol Sci. 2007;57 Suppl:S59]</b>

Journal

  • Proceedings of Annual Meeting of the Physiological Society of Japan

    Proceedings of Annual Meeting of the Physiological Society of Japan 2007(0), 059-059, 2007

    PHYSIOLOGICAL SOCIETY OF JAPAN

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