MACC1 driven alterations in cellular biomechanics facilitate cell motility in glioblastoma.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSION
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. Video Abstract.
['Hohmann|Tim|T|0000-0002-0304-7221', 'Hohmann|Urszula|U|', 'Kolbe|Marc R|MR|', 'Dahlmann|Mathias|M|', 'Kobelt|Dennis|D|', 'Stein|Ulrike|U|', 'Dehghani|Faramarz|F|']
D002448:Cell Adhesion D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D015972:Gene Expression Regulation, Neoplastic D005909:Glioblastoma D006801:Humans D015534:Trans-Activators
MACC1 Biomechanics Glioblastoma Migration Adhesion Elasticity