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

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...

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Main Authors: Armaiz-Pena, Guillermo N. (Author) , Allen, Julie K. (Author) , Cruz, Anthony (Author) , Stone, Rebecca L. (Author) , Nick, Alpa M. (Author) , Lin, Yvonne G. (Author) , Han, Liz Y. (Author) , Mangala, Lingegowda S. (Author) , Villares, Gabriel J. (Author) , Vivas-Mejia, Pablo (Author) , Rodriguez-Aguayo, Cristian (Author) , Nagaraja, Archana S. (Author) , Gharpure, Kshipra M. (Author) , Wu, Zheng (Author) , English, Robert D. (Author) , Soman, Kizhake V. (Author) , Shahzad, Mian M. K. (Author) , Zigler, Maya (Author) , Deavers, Michael T. (Author) , Zien, Alexander (Author) , Soldatos, Theodoros (Author) , Jackson, David B. (Author) , Wiktorowicz, John E. (Author) , Torres-Lugo, Madeline (Author) , Young, Tom (Author) , De Geest, Koen (Author) , Gallick, Gary E. (Author) , Bar-Eli, Menashe (Author) , Lopez-Berestein, Gabriel (Author) , Cole, Steve W. (Author) , Lopez, Gustavo E. (Author) , Lutgendorf, Susan K. (Author) , Sood, Anil K. (Author)
Format: Article (Journal)
Language:English
Published: 29 Jan 2013
In: Nature Communications
Year: 2013, Volume: 4
ISSN:2041-1723
DOI:10.1038/ncomms2413
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/ncomms2413
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/ncomms2413
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Author Notes: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 & Anil K. Sood
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Summary: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.
Item Description:Gesehen am 26.11.2020
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/ncomms2413

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