The regulation of rhoA by stard 13 in focal adhesions is essential for astrocytoma cell motility. (c2013)

Abstract

The World Health Organization estimates that glioblastoma account only for 2% of all cancers. Diagnosis of these types of tumor is often misleading, resulting in a false treatment and fatalities. Astrocytes rarely exhibit metastasis; but high incidence of spreading within the brain is recorded. Cells display different types of actin protrusions, namely, lamellipodias, filopodias, invadopodias, in order to complete the motility cycle. The small Rho GTPases, RhoA, Rac1 and Cdc42 are now widely accepted as having a major role in motility, by cycling between an active and inactive state. StarD13 have been shown to play the role of a GTPase activating protein, for both RhoA and Cdc42. RhoA was tested for its controversial role in the progression of tumors in astrocytoma. First, the ability of StarD13 to control motility was tested. Data show that StarD13, in fact, do regulate motility. The cycle of RhoA and Rac1 GTPases were then investigated as to activation and effect on migration. Data confirm that StarD13 in fact regulate the activation of RhoA, which in turn regulates Rac1 activity. A RhoA Fret biosensor was used to further study RhoA’s activation pattern and localization, which demonstrates that RhoA cycles between active and inactive at the edge of the cell. These Data suggest that StarD13 has an important role in regulating motility in astrocytomas. This effect is achieved by controlling RhoA activity, which in turn impacts Rac1 activity.