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Signal Cross Talks for Sustained MAPK Activation and Cell Migration Mediated by Reactive Oxygen Species: The Involvement in Tumor Progression

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Signal Transduction in Cancer Metastasis

Part of the book series: Cancer Metastasis - Biology and Treatment ((CMBT,volume 15))

Abstract

Signal transduction exerted by the microenvironment around the primary tumor locus may trigger tumor metastasis especially at the migration stage. Sustained mitogen activated protein kinase (MAPK) signaling involved in uncontrolled tumor cell migration rely on the cross talks between integrin, receptor tyrosine kinas (RTK) and protein kinase C (PKC). The molecular mechanisms for cross talking between these migration-related signal cascades leading to sustained cell migration are reviewed, focusing on the focal adhesion scaffold protein paxillin as the platform for signal integration. We proposed reactive oxygen species (ROS) as the critical signal messenger sustaining these signal cascades. For the cross talk of integrin with RTK, ROS may suppress paxillin-associated protein tyrosine phosphatase (PTP-PEST) relieving its negative regulatory effects. For the cross talk of integrin with PKC, PKC itself may phosphorylate integrin or paxillin-associated focal adhesion proteins to induce generation of ROS which may reactivate PKC. In the future, ROS will be validated as the promising therapeutic targets for prevention of tumor metastasis.

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Acknowledgement

We thank the financial support from National Science council in Taiwan for the studies relevant to ROS-mediated signal transduction.

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  1. Research Center for Hepatology, Department of Medicine, Buddhist Tzu Chi General Hospital, School of Medicine and Graduate Institute of Clinical Medicine, Tzu Chi University, Hualien, Taiwan

    Chi-Tan Hu

  2. Department of Medical Technology, Graduate Institute of Medicine, Tzu Chi University, Hualien, Taiwan

    Jia-Ru Wu & Wen-Sheng Wu

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Correspondence to Wen-Sheng Wu .

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  1. Tzu-Chi University, College of Medicine, Institute of medical biotechnology, Chung-Yang Rd, Sec 3 701, Hualien, 970, Taiwan R.O.C.

    Wen-Sheng Wu

  2. Buddhist Tzu-Chi General Hospital, Department of Medicine, Research Center for Hepatology, Chung-Yang Rd, Sec 3 707, Hualien, 970, Taiwan R.O.C.

    Chi-Tan Hu

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Hu, CT., Wu, JR., Wu, WS. (2010). Signal Cross Talks for Sustained MAPK Activation and Cell Migration Mediated by Reactive Oxygen Species: The Involvement in Tumor Progression. In: Wu, WS., Hu, CT. (eds) Signal Transduction in Cancer Metastasis. Cancer Metastasis - Biology and Treatment, vol 15. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9522-0_7

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