Abstract
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 RSU-1 expression levels and invasive capacity and decreasing GDF15 levels to investigate the interplay between RSU-1 and GDF15 with regard to cell invasion. Four experimental approaches were used: (a) GDF15 treatment, (b) Rsu-1 silencing, (c) GDF15 silencing, and (d) combined GDF15 treatment and RSU-1 silencing. We found that the differential expression of RSU-1 and GDF15 in H4 and A172 cells leading to inhibition of cell invasion in H4 cells and promotion in A172 through respective changes in PINCH1, RhoA and MMP-13 expression. Interestingly SW1088, with intermediate RSU-1 and GDF15 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.
Highlights
Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor, which is known to develop from astrocytes and to be associated with poor prognosis and decreased survival rates [1,2]
We wondered whether Ras suppressor 1 (RSU-1) and GDF-15 are collaborating in glioma cell invasion through a common molecular pathway, as both genes are indirectly associated regulating glioma cell invasion through a common molecular pathway, as both genes are indirectly with actin cytoskeleton reorganization and aggressive cancer cellcancer behavior associated with actin cytoskeleton reorganization and aggressive cell [21,45]
We recently demonstrated a differential regulation of cell migration and invasion of glioma cells by RSU-1 based on their aggressiveness, with regulation of cell migration and invasion of glioma cells by RSU-1 based on their aggressiveness, RSU-1 promoting an invasive behavior in aggressive cells (A172 and U87-MG) and inhibiting them with RSU-1 promoting an invasive behavior in aggressive cells (A172 and U87-MG) and inhibiting them in the less aggressive ones (H4 and SW1088) [34]
Summary
Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor, which is known to develop from astrocytes and to be associated with poor prognosis and decreased survival rates [1,2]. It is characterized by the ability of the cells to invade the surrounding brain parenchyma [3,4,5]. Focal adhesion (FA) proteins, localized at cell-ECM adhesion sites maintain direct or indirect connections with actin cytoskeleton [9,10] and they are critically involved in many physiological and pathological processes including the regulation of the migratory and invasive capacity of glioma cells [11,12]. Alterations in the expression or function of FA proteins directly affects the ability of glioma cells to migrate and invade into adjacent tissues of the brain
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