整合素相關(guān)激酶（ILK）是一種多功能的存在于細(xì)胞質(zhì)中的絲氨酸/蘇氨酸激酶,。最近研究表明，ILK表達(dá)增高的癌癥患者存活率低,，預(yù)后差、轉(zhuǎn)移率也升高。
雖然ILK過度表達(dá)的原因仍然有待闡明,，但越來越多的研究發(fā)現(xiàn)了整合素相關(guān)激酶主要通過調(diào)控幾個下游靶蛋白來實現(xiàn)其致癌能力，這些下游蛋白在腫瘤細(xì)胞的增殖,、存活和遷移過程中發(fā)揮作用,。
即使有了前期研究成果，ILK的促腫瘤轉(zhuǎn)移的機制仍然沒有完全得到解釋,。上皮間質(zhì)轉(zhuǎn)化（EMT）是觸發(fā)癌細(xì)胞侵襲和轉(zhuǎn)移的關(guān)鍵事件,。近日Cell Signal雜志刊登的一則論文證實，抑制人源膀胱癌細(xì)胞表達(dá)ILK后,，腫瘤細(xì)胞的生長受到抑制,，凋亡增加。
研究人員推測,，ILK可能涉及在EMT過程中發(fā)揮重要作用,。科研工作者用RNA干擾膀胱癌細(xì)胞ILK的表達(dá),，ILK的抑制能降低波形蛋白,、Snail,、Slug和Twist表達(dá)，升高E-鈣粘素的表達(dá),。
此外,，研究人員發(fā)現(xiàn)，抑制ILK后能抑制腫瘤細(xì)胞增殖,、遷移和侵襲,，也能改變細(xì)胞形態(tài)。研究數(shù)據(jù)還表明,，RNA干擾ILK后抑制下游信號Akt和GSK3beta的磷酸化,，增加nm23-H1基因的表達(dá)，減少腫瘤細(xì)胞MMP-2和MMP-9的表達(dá),。
總之研究結(jié)果揭示ILK是通過調(diào)節(jié)EMT在膀胱癌的發(fā)展中發(fā)揮作用,。ILK可能是一種很有前途的膀胱癌診斷標(biāo)志物和治療靶標(biāo)。（生物谷：Bioon.com)
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.
