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Src activation by β-adrenoreceptors is a key switch for tumor metastasis
Journal article   Open access   Peer reviewed

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

Guillermo N Armaiz-Pena, Julie K Allen, Anthony Cruz, Rebecca L Stone, Alpa M Nick, Yvonne G Lin, Liz Y Han, Lingegowda S Mangala, Gabriel J Villares, Pablo Vivas-Mejia, …
Nature communications, Vol.4, pp.1403-1403
01/01/2013
DOI: 10.1038/ncomms2413
PMID: 23360994
url
https://doi.org/10.1038/ncomms2413View
Published (Version of record) Open Access

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Abstract

Norepinephrine (NE) 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 signaling networks activated in response to beta-adrenergic signaling in cancer cells. These results also identify a new mechanism of Src phosphorylation that mediates beta-adrenergic/PKA regulation of downstream networks, thereby enhancing tumor cell migration, invasion and growth. In human ovarian cancer samples, high tumoral NE levels were correlated with high pSrcY419 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 signaling in the tumor microenvironment.
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