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Screening of a PKC ζ-specific kinase inhibitor PKCzI257.3 which inhibits EGF-induced breast cancer cell chemotaxis

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Summary

Chemotaxis has recently been implicated in tumor metastasis. Protein Kinase C(PKC)ζ is often over-activated and is a key signal transducer shared by both EGFR- and CXCR4-mediated chemotactic signaling in human breast and lung cancers, as well as CSF-1-induced macrophage migration. In order to develop potential inhibitors targeting PKCζ for effective blockage of cancer cell chemotaxis and tumor metastasis, the Z′-LYTE™ KINASE ASSAY -SER/THR 7 PEPTIDE Kit was used and a compound called PKCzI257.3 was identified with IC50 of 28 µM. As a result of treatment, chemotactic migration potency of the human breast cancer cell MDA-MB-231 were impaired, while no significant effect was observed on cell proliferation. Furthermore, EGF-induced cofilin phosphorylation, a critical step of cofilin recycle and actin polymerization, was also dampened, which was relevant to the decreased cell migration. Our results suggest that PKCzI257.3 is a PKCζ-specific compound inhibitor which blocked cancer cell migration and may serve as a potential therapeutic drug for cancer treatment.

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Acknowledgement

The authors thank Tianjin Commission of Science and Technology (06TXTJJC14502), National 973 program (2006CB705600), National 863 program (2006AA02Z190), NSFC (30772528) and NSFC (30772529) for financial supports.

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Authors and Affiliations

  1. Key Laboratory of Breast Cancer Prevention and Therapy of the Ministry of Education; Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China

    Jing Wu, Baogang Zhang, Min Wu, Hongyan Li, Ruifang Niu, Guoguang Ying & Ning Zhang

  2. Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, China

    Ning Zhang

  3. Department of Pathology, Weifang Medical University, Shandong, China

    Baogang Zhang

  4. Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China

    Ruifang Niu & Guoguang Ying

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  1. Jing Wu
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  2. Baogang Zhang
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  3. Min Wu
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  4. Hongyan Li
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  5. Ruifang Niu
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Correspondence to Ruifang Niu or Guoguang Ying.

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Wu, J., Zhang, B., Wu, M. et al. Screening of a PKC ζ-specific kinase inhibitor PKCzI257.3 which inhibits EGF-induced breast cancer cell chemotaxis. Invest New Drugs 28, 268–275 (2010). https://doi.org/10.1007/s10637-009-9242-8

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  • DOI: https://doi.org/10.1007/s10637-009-9242-8

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