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Src activation by β-adrenoreceptors is a key switch for tumour metastasis

Author

Listed:
  • Guillermo N. Armaiz-Pena

    (The University of Texas MD Anderson Cancer Center)

  • Julie K. Allen

    (The University of Texas MD Anderson Cancer Center
    Cancer Biology Program, Graduate School of Biomedical Sciences, The University of Texas Health Science Center)

  • Anthony Cruz

    (University of Puerto Rico)

  • Rebecca L. Stone

    (The University of Texas MD Anderson Cancer Center)

  • Alpa M. Nick

    (The University of Texas MD Anderson Cancer Center)

  • Yvonne G. Lin

    (The University of Texas MD Anderson Cancer Center)

  • Liz Y. Han

    (The University of Texas MD Anderson Cancer Center)

  • Lingegowda S. Mangala

    (The University of Texas MD Anderson Cancer Center
    Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center)

  • Gabriel J. Villares

    (Cancer Biology Program, Graduate School of Biomedical Sciences, The University of Texas Health Science Center
    The University of Texas MD Anderson Cancer Center)

  • Pablo Vivas-Mejia

    (The University of Texas MD Anderson Cancer Center
    Medical Sciences Campus, University of Puerto Rico)

  • Cristian Rodriguez-Aguayo

    (The University of Texas MD Anderson Cancer Center)

  • Archana S. Nagaraja

    (The University of Texas MD Anderson Cancer Center
    Cancer Biology Program, Graduate School of Biomedical Sciences, The University of Texas Health Science Center)

  • Kshipra M. Gharpure

    (The University of Texas MD Anderson Cancer Center
    Cancer Biology Program, Graduate School of Biomedical Sciences, The University of Texas Health Science Center)

  • Zheng Wu

    (Biomolecular Resource Facility, The University of Texas Medical Branch
    The University of Texas Medical Branch)

  • Robert D. English

    (Biomolecular Resource Facility, The University of Texas Medical Branch)

  • Kizhake V. Soman

    (Biomolecular Resource Facility, The University of Texas Medical Branch
    The University of Texas Medical Branch)

  • Mian M. K. Shahzad

    (The University of Texas MD Anderson Cancer Center)

  • Maya Zigler

    (Cancer Biology Program, Graduate School of Biomedical Sciences, The University of Texas Health Science Center
    The University of Texas MD Anderson Cancer Center)

  • Michael T. Deavers

    (The University of Texas MD Anderson Cancer Center)

  • Alexander Zien

    (Molecular Health GmbH)

  • Theodoros G. Soldatos

    (Molecular Health GmbH)

  • David B. Jackson

    (Molecular Health GmbH)

  • John E. Wiktorowicz

    (Biomolecular Resource Facility, The University of Texas Medical Branch
    The University of Texas Medical Branch)

  • Madeline Torres-Lugo

    (University of Puerto Rico)

  • Tom Young

    (Lehman College)

  • Koen De Geest

    (University of Iowa)

  • Gary E. Gallick

    (The University of Texas MD Anderson Cancer Center)

  • Menashe Bar-Eli

    (The University of Texas MD Anderson Cancer Center)

  • Gabriel Lopez-Berestein

    (Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Steve W. Cole

    (University of California)

  • Gustavo E. Lopez

    (University of Puerto Rico)

  • Susan K. Lutgendorf

    (University of Iowa
    and Holden Comprehensive Cancer Center, University of Iowa)

  • Anil K. Sood

    (The University of Texas MD Anderson Cancer Center
    Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

Abstract

Noradrenaline can modulate multiple cellular functions important for cancer progression; however, how this single extracellular signal regulates such a broad array of cellular processes is unknown. Here we identify Src as a key regulator of phosphoproteomic signalling networks activated in response to beta-adrenergic signalling in cancer cells. These results also identify a new mechanism of Src phosphorylation that mediates beta-adrenergic/PKA regulation of downstream networks, thereby enhancing tumour cell migration, invasion and growth. In human ovarian cancer samples, high tumoural noradrenaline levels were correlated with high pSrcY419 levels. Moreover, among cancer patients, the use of beta blockers was significantly associated with reduced cancer-related mortality. Collectively, these data provide a pivotal molecular target for disrupting neural signalling in the tumour microenvironment.

Suggested Citation

  • Guillermo N. Armaiz-Pena & Julie K. Allen & Anthony Cruz & Rebecca L. Stone & Alpa M. Nick & Yvonne G. Lin & Liz Y. Han & Lingegowda S. Mangala & Gabriel J. Villares & Pablo Vivas-Mejia & Cristian Rod, 2013. "Src activation by β-adrenoreceptors is a key switch for tumour metastasis," Nature Communications, Nature, vol. 4(1), pages 1-12, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2413
    DOI: 10.1038/ncomms2413
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