Small molecule inhibition of cytoskeletal dynamics in melanoma tumors results in altered transcriptional expression patterns of key genes involved in tumor initiation and progression.
Small molecule inhibition of cytoskeletal dynamics in melanoma tumors results in altered transcriptional expression patterns of key genes involved in tumor initiation and progression.
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发表时间：
2011-03
影响因子：
2.5
通讯作者：
Carrie Spencer;J. Montalvo;Sarah Mclaughlin;B. Bryan
中科院分区：
文献类型：
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作者：
Carrie Spencer;J. Montalvo;Sarah Mclaughlin;B. Bryan
Rho激酶信号主要通过调节f -肌动蛋白动力学在肿瘤发生过程中发挥重要作用，抑制该途径可减少肿瘤体积和许多肿瘤类型的转移。虽然Rho激酶的细胞骨架调节作用一直是深入研究的主题，但Rho激酶与基因表达改变的机制在很大程度上是未知的。材料和方法对sham或小分子抑制剂Y27632治疗的黑色素瘤进行全局基因表达分析。结果：在黑色素瘤中抑制Rho激酶活性导致94个基因的基因转录发生统计学意义上的显著变化，其中许多基因在肿瘤的发生和进展中起关键作用。结论Rho激酶信号除了通过磷酸化蛋白组调控肿瘤发生外，还参与肿瘤转录组的调控。
BACKGROUND Rho kinase signaling plays an important role in the oncogenic process largely through its regulation of F-actin dynamics, and inhibition of this pathway results in reduction in tumor volume and metastasis across a number of tumor types. While the cytoskeletal-regulatory role of Rho kinase has been a topic of in-depth study, the mechanisms linking Rho kinase to altered gene expression are largely unknown. MATERIALS AND METHODS Global gene expression analysis was performed on melanoma tumors treated with sham or the small molecule inhibitor Y27632. RESULTS Inhibition of Rho kinase activity in melanoma tumors results in a statistically significant change in gene transcription of 94 genes, many of which are critically involved in tumor initiation and progression. CONCLUSION In addition to regulating tumorigenesis through modulation of the phosphoproteome, Rho kinase signaling also contributes to the regulation of the tumor transcriptome.