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Nature Communications
Article . 2013 . Peer-reviewed
License: Springer Nature TDM
Data sources: Crossref
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PubMed Central
Article . 2013
Data sources: PubMed Central
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Src activation by β-adrenoreceptors is a key switch for tumour metastasis

Authors: Guillermo N, Armaiz-Pena; Julie K, Allen; Anthony, Cruz; Rebecca L, Stone; Alpa M, Nick; Yvonne G, Lin; Liz Y, Han; +27 Authors

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

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.

Keywords

Models, Molecular, Ovarian Neoplasms, Adrenergic beta-Antagonists, Cyclic AMP-Dependent Protein Kinases, Article, Enzyme Activation, Mice, Norepinephrine, Phosphoserine, Cell Movement, Cell Line, Tumor, Receptors, Adrenergic, beta, Cyclic AMP, Animals, Humans, Female, Neoplasm Invasiveness, Neoplasm Metastasis, Phosphorylation, Cell Proliferation, Signal Transduction

  • BIP!
    Impact byBIP!
    selected citations
    These citations are derived from selected sources.
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    203
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 1%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
203
Top 1%
Top 10%
Top 1%
Green
gold