The regulation of RhoA at focal adhesions by StarD13 is important for astrocytoma cell motility

Abstract

Malignant astrocytomas are highly invasive into adjacent and distant regions of the normal brain. Rho GTPases are small monomeric G proteins that play important roles in cytoskeleton rearrangement, cell motility, and tumor invasion. In the present study, we show that the knock down of StarD13, a GTPase activating protein (GAP) for RhoA and Cdc42, inhibits astrocytoma cell migration through modulating focal adhesion dynamics and cell adhesion. This effect is mediated by the resulting constitutive activation of RhoA and the subsequent indirect inhibition of Rac. Using Total Internal Reflection Fluorescence (TIRF)-based Förster Resonance Energy Transfer (FRET), we show that RhoA activity localizes with focal adhesions at the basal surface of astrocytoma cells. Moreover, the knock down of StarD13 inhibits the cycling of RhoA activation at the rear edge of cells, which makes them defective in retracting their tail. This study highlights the importance of the regulation of RhoA activity in focal adhesions of astrocytoma cells and establishes StarD13 as a GAP playing a major role in this process.

β-2-himachalen-6-ol: A novel anticancer sesquiterpene unique to the Lebanese wild carrot

“…We suspected that the mechanism of inhibition of migration of β-2-himachalen-6-ol could be due to the inhibition of turnover and disassembly of focal adhesions. Cycling of focal adhesions formation and disassembly will ultimately lead to cellular crawling over the ECM (Hanna and El-Sibai, 2013;Khalil et al, 2014). After observing the effect of β-2-himachalen-6-ol on 2D cell motility we were interested in investigating its effect on 3D migration.…”

Resveratrol suppresses human glioblastoma cell migration and invasion via activation of RhoA/ROCK signaling pathway

“…RhoA, a well-known member of the Rho protein family, has been reported to be significantly underexpressed in astrocytoma and inversely correlated with tumor malignancy (10). The increase of RhoA activity in glioblastoma cells is reportedly linked with impaired cell migration and invasion through the rearrangement of actin into stress fibers and the induction of focal adhesions (12,36). The role of RhoA is mediated through a major effector, ROCK, activation of which has been shown to inhibit migration and invasion of astrocytoma cells (37).…”

Rho regulation: DLC proteins in space and time

“…Interestingly, DLC2 knockdown reduced motility and enhanced adhesion as a consequence of aberrant regulation of RhoA and Rac activity in human astrocytoma cells [35]. This phenotype could be rescued by either downregulating RhoA or overexpressing dominant active Rac1, indicating that RhoA activation upon DLC2 loss indirectly caused Rac1 inhibition.…”