Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Nat Commun. 2013;4:1403. 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.
去甲肾上腺素可以调节多种对癌症进展很重要的细胞功能；然而，这种单一的细胞外信号如何调节如此广泛的细胞过程尚不清楚。在这里，我们鉴定出Src 是一种关键调节剂，可调节在癌细胞中响应β-肾上腺素信号而被激活的磷酸化蛋白质组学信号网络。这些结果还确定了 Src 磷酸化的一种新机制，该机制介导β-肾上腺素/PKA 对下游网络的调节，从而增强肿瘤细胞的迁移、侵袭和生长。在人类卵巢癌样本中，肿瘤中去甲肾上腺素水平较高与 pSrc(Y419)水平较高相关。此外，在癌症患者中，β受体阻滞剂的使用与降低癌症相关死亡率显著相关。总之，这些数据为破坏肿瘤微环境中的神经信号提供了一个关键的分子靶点。
