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

• Published in: Nature communications Vol. 4; no. 1; p. 1403
• Main Authors: Armaiz-Pena, Guillermo N, Allen, Julie K, Cruz, Anthony, Stone, Rebecca L, Nick, Alpa M, Lin, Yvonne G, Han, Liz Y, Mangala, Lingegowda S, Villares, Gabriel J, Vivas-Mejia, Pablo, Rodriguez-Aguayo, Cristian, Nagaraja, Archana S, Gharpure, Kshipra M, Wu, Zheng, English, Robert D, Soman, Kizhake V, Shahzad, Mian M K, Shazhad, Mian M K, Zigler, Maya, Deavers, Michael T, Zien, Alexander, Soldatos, Theodoros G, Jackson, David B, Wiktorowicz, John E, Torres-Lugo, Madeline, Young, Tom, De Geest, Koen, Gallick, Gary E, Bar-Eli, Menashe, Lopez-Berestein, Gabriel, Cole, Steve W, Lopez, Gustavo E, Lutgendorf, Susan K, Sood, Anil K
• Format: Journal Article
• Language: English
• Published: England 01.01.2013
• Subjects: Adrenergic beta-Antagonists - pharmacology; Adrenergic beta-Antagonists - therapeutic use; Animals; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Cyclic AMP - metabolism; Cyclic AMP-Dependent Protein Kinases - metabolism; Enzyme Activation - drug effects; Female; Humans; Mice; Models, Molecular; Neoplasm Invasiveness; Neoplasm Metastasis; Norepinephrine - pharmacology; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - enzymology; Ovarian Neoplasms - mortality; Ovarian Neoplasms - pathology; Phosphorylation - drug effects; Phosphoserine - metabolism; Receptors, Adrenergic, beta - metabolism; Signal Transduction - drug effects; src-Family Kinases - chemistry; src-Family Kinases - metabolism; Stress, Physiological - drug effects; Survival Analysis; Tyrosine - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms2413

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.