Src activation by β-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, 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 and Anil K. Sood ()
Additional contact information
Guillermo N. Armaiz-Pena: The University of Texas MD Anderson Cancer Center
Julie K. Allen: The University of Texas MD Anderson Cancer 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
Gabriel J. Villares: Cancer Biology Program, Graduate School of Biomedical Sciences, The University of Texas Health Science Center
Pablo Vivas-Mejia: The University of Texas MD Anderson Cancer Center
Cristian Rodriguez-Aguayo: The University of Texas MD Anderson Cancer Center
Archana S. Nagaraja: The University of Texas MD Anderson Cancer Center
Kshipra M. Gharpure: The University of Texas MD Anderson Cancer Center
Zheng Wu: Biomolecular Resource Facility, 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
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
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
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
Steve W. Cole: University of California
Gustavo E. Lopez: University of Puerto Rico
Susan K. Lutgendorf: University of Iowa
Anil K. Sood: The University of Texas MD Anderson Cancer Center

Nature Communications, 2013, vol. 4, issue 1, 1-12

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms2413

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