Src activation by β-adrenoreceptors is a key switch for tumour metastasis.
Enviado por Pablo Vivas-Mejia el
Título | Src activation by β-adrenoreceptors is a key switch for tumour metastasis. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Autores | Armaiz-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 |
Journal | Nat Commun |
Volume | 4 |
Pagination | 1403 |
Date Published | 2013 |
ISSN | 2041-1723 |
Palabras clave | Adrenergic 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. |
DOI | 10.1038/ncomms2413 |
Alternate Journal | Nat Commun |
PubMed ID | 23360994 |
PubMed Central ID | PMC3561638 |
Grant List | CA104825 / 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 |