Metastasis-associated in colon cancer 1 (MACC1) is an established marker for metastasis and tumor cell migration in a multitude of tumor entities, including glioblastoma (GBM). Nevertheless, the mechanism underlying the increased migratory capacity in GBM is not comprehensively explored. We performed live cell and atomic force microscopy measurements to assess cell migration and mechanical properties of MACC1 overexpressing GBM cells. We quantified MACC1 dependent dynamics of 3D aggregate formation. For mechanistic studies we measured the expression of key adhesion molecules using qRT-PCR, and MACC1 dependent changes in short term adhesion to fibronectin and laminin. We then determined changes in sub-cellular distribution of integrins and actin in dependence of MACC1, but also in microtubule and intermediate filament organization. MACC1 increased the migratory speed and elastic modulus of GBM cells, but decreased cell-cell adhesion and inhibited the formation of 3D aggregates. These effects were not associated with altered mRNA expression of several key adhesion molecules or altered short-term affinity to laminin and fibronectin. MACC1 did neither change the organization of the microtubule nor intermediate filament cytoskeleton, but resulted in increased amounts of protrusive actin on laminin. MACC1 overexpression increases elastic modulus and migration and reduces adhesion of GBM cells thereby impeding 3D aggregate formation. The underlying molecular mechanism is independent on the organization of microtubules, intermediate filaments and several key adhesion molecules, but depends on adhesion to laminin. Thus, targeting re-organization of the cytoskeleton and cell motility via MACC1 may offer a treatment option to impede GBM spreading.

中文翻译：

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MACC1 驱动的细胞生物力学改变促进胶质母细胞瘤中的细胞运动。

结肠癌转移相关 1 (MACC1) 是包括胶质母细胞瘤 (GBM) 在内的多种肿瘤实体中转移和肿瘤细胞迁移的既定标志物。然而，GBM 迁移能力增加的机制尚未得到全面探讨。我们进行了活细胞和原子力显微镜测量，以评估 MACC1 过表达 GBM 细胞的细胞迁移和机械特性。我们量化了 3D 聚集体形成的 MACC1 依赖性动力学。对于机制研究，我们使用 qRT-PCR 测量了关键粘附分子的表达，以及 MACC1 依赖于纤连蛋白和层粘连蛋白的短期粘附变化。然后，我们确定了依赖 MACC1 的整合素和肌动蛋白亚细胞分布的变化，以及微管和中间丝组织的变化。MACC1 增加了 GBM 细胞的迁移速度和弹性模量，但降低了细胞间粘附并抑制了 3D 聚集体的形成。这些影响与几个关键粘附分子的 mRNA 表达改变或对层粘连蛋白和纤连蛋白的短期亲和力改变无关。MACC1 既没​​有改变微管的组织，也没有改变中间丝细胞骨架，但导致层粘连蛋白上突出的肌动蛋白数量增加。MACC1 过表达会增加弹性模量和迁移，并减少 GBM 细胞的粘附，从而阻碍 3D 聚集体的形成。潜在的分子机制独立于微管、中间丝和几个关键粘附分子的组织，但取决于对层粘连蛋白的粘附。因此，