Src activation by adrenoreceptors is a key switch for tumour metastasis

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 Rodriguez-Aguayo, Archana S. Nagaraja, Kshipra M. Gharpure, Zheng Wu, Robert D. English, Kizhake V. Soman, Mian M K Shahzad, Maya Zigler, Michael T. Deavers, Alexander Zien & 13 others Theodoros G. Soldatos, David B. Jackson, John E. Wiktorowicz, Madeline Torres-Lugo, Tom Young, Koen De Geest, Gary E. Gallick, Menashe Bar-Eli, Gabriel Lopez-Berestein, Steve W. Cole, Gustavo E. Lopez, Susan K. Lutgendorf, Anil K. Sood

    Research output: Contribution to journalArticle

    106 Citations (Scopus)

    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 pSrc Y419 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.

    Original languageEnglish (US)
    Article number1403
    JournalNature Communications
    Volume4
    DOIs
    StatePublished - 2013

    Fingerprint

    metastasis
    Tumors
    tumors
    switches
    cancer
    Chemical activation
    Switches
    activation
    Neoplasm Metastasis
    Adrenergic Agents
    adrenergics
    Norepinephrine
    Cells
    Neoplasms
    Phosphorylation
    disrupting
    phosphorylation
    Tumor Microenvironment
    mortality
    regulators

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Chemistry(all)
    • Physics and Astronomy(all)

    Cite this

    Armaiz-Pena, G. N., Allen, J. K., Cruz, A., Stone, R. L., Nick, A. M., Lin, Y. G., ... Sood, A. K. (2013). Src activation by adrenoreceptors is a key switch for tumour metastasis. Nature Communications, 4, [1403]. https://doi.org/10.1038/ncomms2413

    Src activation by adrenoreceptors is a key switch for tumour metastasis. / Armaiz-Pena, Guillermo N.; Allen, Julie K.; Cruz, Anthony; Stone, Rebecca L.; Nick, Alpa M.; Lin, Yvonne G.; Han, Liz Y.; Mangala, Lingegowda S.; Villares, Gabriel J.; Vivas-Mejia, Pablo; Rodriguez-Aguayo, Cristian; Nagaraja, Archana S.; Gharpure, Kshipra M.; Wu, Zheng; English, Robert D.; Soman, Kizhake V.; Shahzad, Mian M K; Zigler, Maya; Deavers, Michael T.; Zien, Alexander; Soldatos, Theodoros G.; Jackson, David B.; Wiktorowicz, John E.; Torres-Lugo, Madeline; Young, Tom; De Geest, Koen; Gallick, Gary E.; Bar-Eli, Menashe; Lopez-Berestein, Gabriel; Cole, Steve W.; Lopez, Gustavo E.; Lutgendorf, Susan K.; Sood, Anil K.

    In: Nature Communications, Vol. 4, 1403, 2013.

    Research output: Contribution to journalArticle

    Armaiz-Pena, GN, Allen, JK, Cruz, A, Stone, RL, Nick, AM, Lin, YG, Han, LY, Mangala, LS, Villares, GJ, Vivas-Mejia, P, Rodriguez-Aguayo, C, Nagaraja, AS, Gharpure, KM, Wu, Z, English, RD, Soman, KV, Shahzad, MMK, Zigler, M, Deavers, MT, Zien, A, Soldatos, TG, Jackson, DB, Wiktorowicz, JE, Torres-Lugo, M, Young, T, De Geest, K, Gallick, GE, Bar-Eli, M, Lopez-Berestein, G, Cole, SW, Lopez, GE, Lutgendorf, SK & Sood, AK 2013, 'Src activation by adrenoreceptors is a key switch for tumour metastasis', Nature Communications, vol. 4, 1403. https://doi.org/10.1038/ncomms2413
    Armaiz-Pena GN, Allen JK, Cruz A, Stone RL, Nick AM, Lin YG et al. Src activation by adrenoreceptors is a key switch for tumour metastasis. Nature Communications. 2013;4. 1403. https://doi.org/10.1038/ncomms2413
    Armaiz-Pena, Guillermo N. ; Allen, Julie K. ; Cruz, Anthony ; Stone, Rebecca L. ; Nick, Alpa M. ; Lin, Yvonne G. ; Han, Liz Y. ; Mangala, Lingegowda S. ; Villares, Gabriel J. ; Vivas-Mejia, Pablo ; Rodriguez-Aguayo, Cristian ; Nagaraja, Archana S. ; Gharpure, Kshipra M. ; Wu, Zheng ; English, Robert D. ; Soman, Kizhake V. ; Shahzad, Mian M K ; Zigler, Maya ; Deavers, Michael T. ; Zien, Alexander ; Soldatos, Theodoros G. ; Jackson, David B. ; Wiktorowicz, John E. ; Torres-Lugo, Madeline ; Young, Tom ; De Geest, Koen ; Gallick, Gary E. ; Bar-Eli, Menashe ; Lopez-Berestein, Gabriel ; Cole, Steve W. ; Lopez, Gustavo E. ; Lutgendorf, Susan K. ; Sood, Anil K. / Src activation by adrenoreceptors is a key switch for tumour metastasis. In: Nature Communications. 2013 ; Vol. 4.
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