ANLN plays a critical role in human lung carcinogenesis through the activation of RHOA and by involvement in the phosphoinositide 3-kinase/AKT pathway
ANLN plays a critical role in human lung carcinogenesis through the activation of RHOA and by involvement in the phosphoinositide 3-kinase/AKT pathway
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DOI：
10.1158/0008-5472.can-05-1507
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发表时间：
2005-12-15
期刊：
影响因子：
11.2
通讯作者：
Nakamura, Y
中科院分区：
文献类型：
--
作者：
Suzuki, C;Daigo, Y;Nakamura, Y
非小细胞肺癌（NSCLC）的基因表达谱分析和随后的功能分析表明，人类ANLN，一个同系物的苯胺，肌动蛋白结合蛋白在果蝇，是反式激活的肺癌细胞，似乎在肺癌的发生中发挥了重要作用。在NSCLC细胞中诱导针对ANLN的小干扰RNA抑制其表达并导致生长抑制;此外，用小干扰RNA处理产生具有较大形态和多个核的细胞，其随后死亡。另一方面，外源性ANLN表达的诱导增强了哺乳动物细胞的迁移能力，通过与RHOA，一个小的鸟苷三磷酸酶，诱导肌动蛋白应力纤维。有趣的是，在NSCLC细胞中磷酸肌醇3-激酶/AKT活性的抑制降低了ANLN的稳定性，并导致细胞核ANLN水平的降低。肺癌组织芯片上的核ANLN免疫组化染色与NSCLC患者的生存率相关，表明该分子可能作为预后指标。我们的数据表明，上调ANLN是一个共同的特点，在肺组织中的致癌过程，并表明，选择性抑制ANLN可能是一个很有前途的方法，开发一种新的策略来治疗肺癌。
Gene expression profile analysis of non-small cell lung cancers (NSCLC) and subsequent functional analyses revealed that human ANLN, a homologue of anillin, an actin-binding protein in Drosophila, was transactivated in lung cancer cells and seemed to play a significant role in pulmonary carcinogenesis. Induction of small interfering RNAs against ANLN in NSCLC cells suppressed its expression and resulted in growth suppression; moreover, treatment with small interfering RNA yielded cells with larger morphology and multiple nuclei, which subsequently died. On the other hand, induction of exogenous expression of ANLN enhanced the migrating ability of mammalian cells by interacting with RHOA, a small guanosine triphosphatase, and inducing actin stress fibers. Interestingly, inhibition of phosphoinositide 3-kinase/AKT activity in NSCLC cells decreased the stability of ANLN and caused a reduction of the nuclear ANLN level. Immunohistochemical staining of nuclear ANLN on lung cancer tissue microarrays was associated with the poor survival of NSCLC patients, indicating that this molecule might serve as a prognostic indicator. Our data imply that up-regulation of ANLN is a common feature of the carcinogenetic process in lung tissue, and suggests that selective suppression of ANLN could be a promising approach for developing a new strategy to treat lung cancers.