The virus-induced protein APOBEC3G inhibits anoikis by activation of Akt kinase in pancreatic cancer cells.
The virus-induced protein APOBEC3G inhibits anoikis by activation of Akt kinase in pancreatic cancer cells.
复制标题
病毒诱导的蛋白 APOBEC3G 通过激活胰腺癌细胞中的 Akt 激酶来抑制失巢凋亡。
DOI：
10.1038/srep12230
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发表时间：
2015-07-16
影响因子：
4.6
通讯作者：
Cai JT
中科院分区：
文献类型：
--
作者：
Wu J;Pan TH;Xu S;Jia LT;Zhu LL;Mao JS;Zhu YL;Cai JT
胰腺癌是最常见的癌症之一，预后较差。有些癌症与病毒感染有关。APOBEC3G（A3G）作为一种病毒诱导蛋白，具有广泛的抗病毒能力，但其在胰腺癌中的作用尚不清楚。采用TaqMan实时定量PCR、免疫组化和免疫荧光染色检测胰腺癌组织中A3G的表达。随后，使用肿瘤异种移植模型在体内评估A3G在胰腺癌中的作用。体外克隆形成实验和流式细胞术检测失巢凋亡。采用免疫共沉淀法和免疫印迹法检测Akt激酶活性和靶蛋白PTEN。胰腺癌组织中病毒诱导蛋白A3G表达显著上调，A3G表达上调促进了异种移植瘤的形成。A3G通过与C2张力蛋白型和PDZ结构域结合使PTEN失活，从而通过Akt活化诱导失巢凋亡抗性。我们的研究结果表明，A3G在胰腺癌细胞中的上调诱导失巢凋亡抵抗，他们提供了新的见解A3G影响胰腺癌细胞的恶性行为的机制。
Pancreatic cancer is one of the more common cancers with a poor prognosis. Some varieties of cancer are related to virus infection. As a virus-induced protein, APOBEC3G (A3G) presents extensive anti-virus ability, but the role of A3G in pancreatic cancer was previously unknown. The expression of A3G in pancreatic cancer was examined using TaqMan real-time qPCR, immunohistochemical and immunofluorescent staining. Subsequently, the role of A3G in pancreatic cancer was evaluated in vivo using the tumor xenograft model. Anoikis was detected by colony formation assay and flow cytometry in vitro. The Akt kinase activity and target protein PTEN were examined by co-immunoprecipitation and immunoblot. The virus-induced protein A3G was significantly up-regulated in pancreatic cancer, and the up-regulation of A3G promoted xenograft tumor formation. A3G inactivated PTEN by binding to the C2 tensin-type and PDZ domains, thereby inducing anoikis resistance through Akt activation. Our results demonstrate that the up-regulation of A3G in pancreatic cancer cells induces anoikis resistance, and they provide novel insight into the mechanism by which A3G affects the malignant behavior of pancreatic cancer cells.