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

Imagen de Pablo Vivas-Mejia
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TítuloSrc activation by β-adrenoreceptors is a key switch for tumour metastasis.
Publication TypeJournal Article
Year of Publication2013
AutoresArmaiz-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, Shazhad, 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
JournalNat Commun
Volume4
Pagination1403
Date Published2013
ISSN2041-1723
Palabras claveAdrenergic beta-Antagonists, Animals, Cell Line, Tumor, Cell Movement, Cell Proliferation, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, Enzyme Activation, Female, Humans, Mice, Models, Molecular, Neoplasm Invasiveness, Neoplasm Metastasis, Norepinephrine, Ovarian Neoplasms, Phosphorylation, Phosphoserine, Receptors, Adrenergic, beta, Signal Transduction, src-Family Kinases, Stress, Physiological, Survival Analysis, Tyrosine
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.

DOI10.1038/ncomms2413
Alternate JournalNat Commun
PubMed ID23360994
PubMed Central IDPMC3561638
Grant ListCA104825 / CA / NCI NIH HHS / United States
CA109298 / CA / NCI NIH HHS / United States
CA110793 / CA / NCI NIH HHS / United States
CA128797 / CA / NCI NIH HHS / United States
CA140933 / CA / NCI NIH HHS / United States
F31 CA126474 / CA / NCI NIH HHS / United States
F31CA126474 / CA / NCI NIH HHS / United States
HV-10-05_(2) / HV / NHLBI NIH HHS / United States
P30 CA016672 / CA / NCI NIH HHS / United States
P30 CA086862 / CA / NCI NIH HHS / United States
P50 CA083639 / CA / NCI NIH HHS / United States
P50 CA098258 / CA / NCI NIH HHS / United States
P50 CA140388 / CA / NCI NIH HHS / United States
P50CA083639 / CA / NCI NIH HHS / United States
P50CA098258 / CA / NCI NIH HHS / United States
R01 CA109298 / CA / NCI NIH HHS / United States
R01 CA110793 / CA / NCI NIH HHS / United States
R01 CA128797 / CA / NCI NIH HHS / United States
R01 CA140933 / CA / NCI NIH HHS / United States
RC2 GM092599 / GM / NIGMS NIH HHS / United States
RC2GM092599 / GM / NIGMS NIH HHS / United States
SC3 GM095417 / GM / NIGMS NIH HHS / United States
T32 CA101642 / CA / NCI NIH HHS / United States
T32 CA101642 / CA / NCI NIH HHS / United States
U54 CA096297 / CA / NCI NIH HHS / United States
U54 CA096300 / CA / NCI NIH HHS / United States
U54 CA151668 / CA / NCI NIH HHS / United States
U54CA151668 / CA / NCI NIH HHS / United States
U54CA96297 / CA / NCI NIH HHS / United States
U54CA96300 / CA / NCI NIH HHS / United States