TY - JOUR
T1 - Src activation by adrenoreceptors is a key switch for tumour metastasis
AU - Armaiz-Pena, Guillermo N.
AU - Allen, Julie K.
AU - Cruz, Anthony
AU - Stone, Rebecca L.
AU - Nick, Alpa M.
AU - Lin, Yvonne G.
AU - Han, Liz Y.
AU - Mangala, Lingegowda S.
AU - Villares, Gabriel J.
AU - Vivas-Mejia, Pablo
AU - Rodriguez-Aguayo, Cristian
AU - Nagaraja, Archana S.
AU - Gharpure, Kshipra M.
AU - Wu, Zheng
AU - English, Robert D.
AU - Soman, Kizhake V.
AU - Shahzad, Mian M K
AU - Zigler, Maya
AU - Deavers, Michael T.
AU - Zien, Alexander
AU - Soldatos, Theodoros G.
AU - Jackson, David B.
AU - Wiktorowicz, John E.
AU - Torres-Lugo, Madeline
AU - Young, Tom
AU - De Geest, Koen
AU - Gallick, Gary E.
AU - Bar-Eli, Menashe
AU - Lopez-Berestein, Gabriel
AU - Cole, Steve W.
AU - Lopez, Gustavo E.
AU - Lutgendorf, Susan K.
AU - Sood, Anil K.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms2413
DO - 10.1038/ncomms2413
M3 - Article
C2 - 23360994
AN - SCOPUS:84877058177
VL - 4
JO - Nat Commun
JF - Nat Commun
SN - 2041-1723
M1 - 1403
ER -