β2-adrenergic receptor signaling promotes pancreatic ductal adenocarcinoma (PDAC) progression through facilitating PCBP2-dependent c-myc expression
β2-adrenergic receptor signaling promotes pancreatic ductal adenocarcinoma (PDAC) progression through facilitating PCBP2-dependent c-myc expression
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β2-肾上腺素能受体信号传导通过促进 PCBP2 依赖性 c-myc 表达促进胰腺导管腺癌 (PDAC) 进展
DOI：
10.1016/j.canlet.2016.01.026
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发表时间：
2016-01-01
期刊：
影响因子：
9.7
通讯作者：
Shen, Aiguo
中科院分区：
文献类型：
--
作者：
Wan, Chunhua;Gong, Chen;Shen, Aiguo
β 2-肾上腺素能受体（β 2-AR）在胰腺导管腺癌（PDAC）进展中起着至关重要的作用。在这份报告中，我们确定聚（rC）结合蛋白2（PCBP 2）作为一种新的结合伴侣的β 2-AR免疫沉淀-质谱（IP-MS）的方法。β 2-AR和PCBP 2之间的关联使用相互免疫沉淀进行验证。重要的是，我们发现在Panc-1和Bxpc 3 PDAC细胞中，在β 2-AR激动剂存在下，两种蛋白质存在显著的相互作用和共定位。β 2-AR诱导的PCBP 2募集导致PDAC细胞中c-myc蛋白水平增加，这可能是由于内部核糖体进入片段（IRES）介导的c-myc翻译增强的结果。β 2-AR的激活促进了细胞增殖和集落形成，而PCBP 2或c-myc的敲低抑制了这种作用。此外，与正常胰腺导管上皮细胞和非癌组织相比，在人PDAC细胞系和组织标本中分别观察到PCBP 2的过表达。β 2-AR和PCBP 2的过度表达与PDAC患者的晚期肿瘤分期和预后显著恶化相关。我们的研究结果阐明了一种新的分子机制，β 2-AR信号通过触发PCBP 2依赖的c-myc表达促进PDAC进展。(C)2016爱思唯尔爱尔兰有限公司版权所有。
The beta 2-adrenergic receptor (beta 2-AR) plays a crucial role in pancreatic ductal adenocarcinoma (PDAC) progression. In this report, we identified poly(rC)-binding protein 2 (PCBP2) as a novel binding partner for beta 2-AR using immunoprecipitation-mass spectrometry (IP-MS) approach. The association between beta 2-AR and PCBP2 was verified using reciprocal immunoprecipitation. Importantly, we found significant interaction and co-localization of the two proteins in the presence of beta 2-AR agonist in Panc-1 and Bxpc3 PDAC cells. beta 2-AR-induced recruitment of PCBP2 led to augmented protein level of c-myc in PDAC cells, likely as a result of enhanced internal ribosome entry segment (IRES)-mediated translation of c-myc. The activation of beta 2-AR accelerated cell proliferation and colony formation, while knockdown of PCBP2 or c-myc restrained the effect. Furthermore, overexpression of PCBP2 was observed in human PDAC cell lines and tissue specimens compared to the normal pancreatic ductal epithelial cells and the non-cancerous tissues respectively. Overexpression of beta 2-AR and PCBP2 was associated with advanced tumor stage and significantly worsened prognosis in patients with PDAC. Our results elucidate a new molecular mechanism by which beta 2-AR signaling facilitates PDAC progression through triggering PCBP2-dependent c-myc expression. (C) 2016 Elsevier Ireland Ltd. All rights reserved.