| Summary: | Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor due to its invasive phenotype. Ras suppressor 1 (RSU-1) is a cell-extracellular matrix adhesion protein and we recently found that it promotes cell invasion in aggressive cells and inhibits it in non-invasive. Growth differentiation factor-15 (GDF15) is known to be involved in actin cytoskeleton reorganization and metastasis. In this study, we used three brain cell lines (H4, SW1088 and A172) with increasing <i>RSU-1</i> expression levels and invasive capacity and decreasing <i>GDF15</i> levels to investigate the interplay between RSU-1 and GDF15 with regard to cell invasion. Four experimental approaches were used: (a) GDF15 treatment, (b) <i>Rsu-1</i> silencing, (c) <i>GDF15</i> silencing, and (d) combined GDF15 treatment and <i>RSU-1</i> silencing. We found that the differential expression of <i>RSU-1</i> and <i>GDF15</i> in H4 and A172 cells leading to inhibition of cell invasion in H4 cells and promotion in A172 through respective changes in <i>PINCH1</i>, <i>RhoA</i> and <i>MMP-13</i> expression. Interestingly SW1088, with intermediate <i>RSU-1</i> and <i>GDF15</i> expression, were not affected by any treatment. We conclude that there is a strong connection between RSU-1 and GDF15 in H4, SW1088 and A172 cells and the relative expression of these two proteins is fundamental in affecting their invasive fate.
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