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Roles of activated Src and Stat3 signaling in melanoma tumor cell growth

Oncogene volume 21, pages 7001–7010 (2002)Cite this article

Abstract

Activation of protein tyrosine kinases is prevalent in human cancers and previous studies have demonstrated that Stat3 signaling is a point of convergence for many of these tyrosine kinases. Moreover, a critical role for constitutive activation of Stat3 in tumor cell proliferation and survival has been established in diverse cancers. However, the oncogenic signaling pathways in melanoma cells remain to be fully defined. In this study, we demonstrate that Stat3 is constitutively activated in a majority of human melanoma cell lines and tumor specimens examined. Blocking Src tyrosine kinase activity, but not EGF receptor or JAK family kinases, leads to inhibition of Stat3 signaling in melanoma cell lines. Consistent with a role of Src in the pathogenesis of melanoma, we show that c-Src tyrosine kinase is activated in melanoma cell lines. Significantly, melanoma cells undergo apoptosis when either Src kinase activity or Stat3 signaling is inhibited. Blockade of Src or Stat3 is also accompanied by down-regulation of expression of the anti-apoptotic genes, Bcl-xL and Mcl-1. These findings demonstrate that Src-activated Stat3 signaling is important for the growth and survival of melanoma tumor cells.

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Acknowledgements

This work was supported by National Institutes of Health Grants (CA75243, CA89693, CA55652 and CA82533) and by the Dr Tsai-Fan Yu Cancer Research Endowment. We thank Drs George Blanck and Suzanne Topalian for melanoma cell lines, Andy Laudano for phospho-Src antibodies, Anita Larson for assisting with preparation of the manuscript. This work was supported in part by the Flow Cytometry Core Facility, Statistical Core Facility, Clinical Trials Facility, Translational Research Laboratory and Image Core Facility at the H Lee Moffitt Cancer Center & Research Institute.

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Authors and Affiliations

  1. Department of Oncology, Immunology Program, H Lee Moffitt Cancer Center and Research Institute, University of South Florida College of Medicine, Tampa, 33612, Florida, FL, USA

    Guilian Niu & Hua Yu

  2. Department of Oncology, Molecular Oncology Program, H Lee Moffitt Cancer Center and Research Institute, University of South Florida College of Medicine, Tampa, 33612, Florida, FL, USA

    Tammy Bowman, Mei Huang & Richard Jove

  3. Department of Oncology, Cutaneous Oncology Program, H Lee Moffitt Cancer Center and Research Institute, University of South Florida College of Medicine, Tampa, 33612, Florida, FL, USA

    Steve Shivers, Douglas Reintgen & Adil Daud

  4. Department of Surgery, University of Michigan Medical School, Ann Arbor, 48105, Michigan, MI, USA

    Alfred Chang

  5. Department of Cancer Research, Pfizer Global Research, Ann Arbor, 48106, Michigan, MI, USA

    Alan Kraker

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  1. Guilian Niu
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Niu, G., Bowman, T., Huang, M. et al. Roles of activated Src and Stat3 signaling in melanoma tumor cell growth. Oncogene 21, 7001–7010 (2002). https://doi.org/10.1038/sj.onc.1205859

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