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.
N1 - Funding Information:
GNA-P was supported, in part, by the NCI F31CA126474 Fellowship for Minority Students. Y.G.L., L.Y.H., A.M.N. and R.L.S. were supported by an NIH T32 Training Grant CA101642. S.K.L. was supported by NIH grants CA140933 and CA104825. M.M.S. was supported by the GCF-Molly Cade ovarian cancer research grant and the NIH/ NICHD Baylor WRHR scholarship grant. This work was also supported in part by NIH grants (CA110793 and CA109298, P50CA083639, P50CA098258, CA128797, RC2GM092599, U54CA151668, U54CA96300 and U54CA96297), the University of Texas Medical Branch NHLBI Proteomics Centre (contract HV-10-05_(2)), Ovarian Cancer Research Fund Programme Project Development Grant, Department of Defence (OC073399, W81XWH-10-1-0158, OC100237 and BC085265), the Zarrow Foundation, the Betty Ann Asche Murray Distinguished Professorship, the Marcus Foundation, the RGK Foundation, the Gilder Foundation, the estate of C.G. Johnson Jr, the Laura and John Arnold Foundation) and the Blanton-Davis Ovarian Cancer Research Programme. The authors thank Ms Donna Reynolds and Drs Robert Langley, and Philip Stork for helpful discussions, comments and for providing reagents. We would like to thank the High Performance Computing Facility of the University of Puerto Rico for the computer time.
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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UR - http://www.scopus.com/inward/citedby.url?scp=84877058177&partnerID=8YFLogxK
U2 - 10.1038/ncomms2413
DO - 10.1038/ncomms2413
M3 - Article
C2 - 23360994
AN - SCOPUS:84877058177
SN - 2041-1723
VL - 4
JO - Nature communications
JF - Nature communications
M1 - 1403
ER -