Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor and it is associated with poor survival. Integrin-linked kinase (ILK) is a serine/threonine protein pseudo-kinase that binds to the cytoplasmic domains of β1 and β3 integrins and has been previously shown to promote invasion and metastasis in many cancer types, including GBM. However, little is known regarding the exact molecular mechanism implicating ILK in GBM aggressiveness. In this study, we used two brain cell lines, the non-invasive neuroglioma H4 cells, and the highly invasive glioblastoma A172 cells, which express ILK in much higher levels than H4. We studied the effect of ILK silencing on the metastatic behavior of glioblastoma cells in vitro and elucidate the underlying molecular mechanism. We showed that siRNA-mediated silencing of ILK inhibits cell migration and invasion of the highly invasive A172 cells while it does not affect the migratory and invasive capacity of H4 cells. These data were also supported by respective changes in the expression of Rho-associated kinase 1 (ROCK1), fascin actin-bundling protein 1 (FSCN1), and matrix metalloproteinase 13 (MMP13), which are known to regulate cell migration and invasion. Our findings were further corroborated by analyzing the Cancer Genome Atlas Glioblastoma Multiforme (TCGA-GBM) dataset. We conclude that ILK promotes glioblastoma cell invasion through activation of ROCK1 and FSCN1 in vitro, providing a more exact molecular mechanism for its action.

多形胶质母细胞瘤（GBM）是脑肿瘤中最具侵略性的一种，它与生存期差有关。整联蛋白连接激酶（ILK）是一种丝氨酸/苏氨酸蛋白假激酶，可与β1和β3整联蛋白的胞质域结合，先前已证明可促进包括GBM在内的许多癌症类型的侵袭和转移。然而，关于ILK参与GBM攻击的确切分子机制知之甚少。在这项研究中，我们使用了两种脑细胞系，即非侵袭性神经胶质瘤H4细胞和高度侵袭性胶质母细胞瘤A172细胞，它们表达ILK的水平远高于H4。我们研究了ILK的作用沉默胶质母细胞瘤细胞的体外转移行为，并阐明其潜在的分子机制。我们表明，siRNA介导的ILK沉默抑制细胞迁移和高侵袭性A172细胞的侵袭，而它不影响H4细胞的迁移和侵袭能力。这些数据还通过在表达相应的变化支持Rho相关激酶1（ROCK1），肌动蛋白集束蛋白1（FSCN1），和基质金属蛋白酶13（MMP13），已知其可调节细胞迁移和侵袭。通过分析癌症基因组图谱多形性胶质母细胞瘤（TCGA-GBM）数据集，进一步证实了我们的发现。我们得出结论，ILK通过激活ROCK1和FSCN1在体外促进胶质母细胞瘤细胞侵袭，为其作用提供了更精确的分子机制。