Beta Adrenoreceptor – Src Kinase Signaling As a Trigger for Cancer Metastasis

Beta Adrenoreceptor – Src Kinase Signaling As a Trigger for Cancer Metastasis

In the July 2013 issue of Nature Communications, Armaiz-Pena et al. demonstrate that stress is able through activation of beta-adrenergic signaling in tumor cells to trigger a critical phosphorylation event, resulting in Src kinase activation, which in turn, can affect tumor growth and metastasis.

Building on previous work showing that sympathetic nervous system activity can promote tumor cell invasion and associated angiogenesis in ovarian carcinoma, the authors sought to further define the signaling pathway involved.

The Src protein was the first tyrosine kinase to be discovered, and is known to be involved in cancer progression. In this study, Src activation in human ovarian cancer cells increased with norepinephrine exposure in the presence of beta-adrenergic receptors.

In turn, Src activation led to enhanced induction of genes associated with tumor migration and invasion. Of note, norepinephrine (NE) is the most abundant stress mediator in the ovary, and in this study, in human ovarian cancer samples, high tumoral NE levels were correlated with high pSrcY419 levels.

Furthermore, in a mouse stress model, stressed animals exhibited greater tumor growth, but propranolol treatment limited this effect, further highlighting the role of beta-adrenergic receptors.

As a clinical correlation, the authors used adverse events data to demonstrate that beta-blocker treatment in cancer patients was associated with a decreased in mortality.

This study reinforces the pivotal role of stress in cancer progression and suggests that readily available therapeutic modalities may be greatly efficacious as an adjunctive cancer treatment.

Source: Nat Commun, 2013; 4:1403. doi: 10.1038/ncomms2413.
Read More: National Library of Medicine

Source: Cover Image: Cancer cell migrating through blood vessel. Credit: Annie Cavanagh, Wellcome Images.

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