Cell Signal：下调整合素相关激酶表达抑制膀胱癌细胞转移

整合素相关激酶（ILK）是一种多功能的存在于细胞质中的丝氨酸/苏氨酸激酶。最近研究表明，ILK表达增高的癌症患者存活率低，预后差、转移率也升高。

虽然ILK过度表达的原因仍然有待阐明，但越来越多的研究发现了整合素相关激酶主要通过调控几个下游靶蛋白来实现其致癌能力，这些下游蛋白在肿瘤细胞的增殖、存活和迁移过程中发挥作用。

即使有了前期研究成果，ILK的促肿瘤转移的机制仍然没有完全得到解释。上皮间质转化（EMT）是触发癌细胞侵袭和转移的关键事件。近日Cell Signal杂志刊登的一则论文证实，抑制人源膀胱癌细胞表达ILK后，肿瘤细胞的生长受到抑制，凋亡增加。

研究人员推测，ILK可能涉及在EMT过程中发挥重要作用。科研工作者用RNA干扰膀胱癌细胞ILK的表达，ILK的抑制能降低波形蛋白、Snail、Slug和Twist表达，升高E-钙粘素的表达。

此外，研究人员发现，抑制ILK后能抑制肿瘤细胞增殖、迁移和侵袭，也能改变细胞形态。研究数据还表明，RNA干扰ILK后抑制下游信号Akt和GSK3beta的磷酸化，增加nm23-H1基因的表达，减少肿瘤细胞MMP-2和MMP-9的表达。

总之研究结果揭示ILK是通过调节EMT在膀胱癌的发展中发挥作用。ILK可能是一种很有前途的膀胱癌诊断标志物和治疗靶标。

doi:10.1016/j.cellsig.2012.02.013
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Downregulation of integrin-linked kinase inhibits epithelial-to-mesenchymaltransition and metastasis in bladder cancer cells.

Zhu J, Pan X, Zhang Z, Gao J, Zhang L, Chen J.

Integrin-linked kinase (ILK) is a multifunctional serine/threonine kinase in cytoplasm. Recent studies showed that cancer patients with increased ILK expression had low survival, poor prognosis and increased metastasis. Although the causes of ILK overexpression remain to be fully elucidated, accumulating evidence suggests that its oncogenic capacity derives from its regulation of several downstream targets that provide cells with signals that promote proliferation, survival and migration. However, the mechanisms underlying tumor metastasis by ILK is still not fully understood. Epithelial–mesenchymal transition (EMT) is a critical event of cancer cells that triggers invasion and metastasis. We recently reported that knockdown of ILK inhibited the growth and induced apoptosis in human bladder cancer cells. Therefore, we postulate that ILK might involve in EMT. Here we further investigate the function of ILK with RNA interference in bladder cancer cells. Knockdown of ILK impeded an EMT with low Vimentin, Snail, Slug and Twist as well as high E-cadherin expression in vivo and vitro. In addition, we found that knockdown of ILK inhibited cell proliferation, migration and invasion as well as changed cell morphology, adhesion and rearranged cytoskeleton in vitro. We also demonstrated that ILK siRNA inhibited phosphorylation of downstream signaling targets Akt and GSK3β, increased expression of nm23-H1, as well as reduced expression of MMP-2 and MMP-9 in vivo and vitro. Furthermore, downregulation of ILK could increase expression of Ribonuclease inhibitor (RI), an important acidic cytoplasmic protein with many functions. Finally, the effects of ILK siRNA on bladder cancer cell phenotype and invasiveness translate into suppression for tumorigenesis and metastasis in vivo. Taken together, our findings highlight that ILK signaling pathway plays a novel role in the development of bladder cancer through regulating EMT. ILK could be a promising diagnostic marker and therapeutic target for bladder cancer.