ABSTRACT
Malignant glioma invasion is a primary cause of brain cancer treatment failure, yet the molecular mechanisms underlying its regulation remain elusive. We developed a novel functional-screening strategy and identified downregulated in renal cell carcinoma (DRR) as a regulator of invasion. We show that DRR drives invasion in vitro and in vivo. We found that while DRR is not expressed in normal glial cells, it is highly expressed in the invasive component of gliomas. Exploring underlying mechanisms, we show that DRR associates with and organizes the actin and microtubular cytoskeletons and that these associations are essential for focal adhesion (FA) disassembly and cell invasion. These findings identify DRR as a new cytoskeletal crosslinker that regulates FA dynamics and cell movement.
Subject(s)
Brain Neoplasms/pathology , Cell Adhesion/physiology , Focal Adhesions/pathology , Glioma/pathology , Nuclear Proteins/metabolism , Animals , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Cell Adhesion/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Movement/physiology , Cytoskeleton/genetics , Cytoskeleton/metabolism , Cytoskeleton/physiology , Focal Adhesions/genetics , Focal Adhesions/metabolism , Genes, Tumor Suppressor , Glioma/genetics , Glioma/metabolism , Humans , Mice , RatsABSTRACT
Leaves from several Passiflora species are largely employed in the Brazilian folk medicine for its anxiolytic and sedative properties. In behavioral studies, to analyze the tranquillizer action of Passiflora actinia Hooker, it was noteworthy that animals treated with the hydroethanol (HE) and methanol (ME) extracts presented an abnormal postural immobility compared to control animals. That observation led to an investigation of the effects of HE and its fractions on evaluation of catalepsy in mice. The results showed that HE extract, methanol extract, the sequent aqueous crude fractions (AF), and fa, fb and fc chromatographic fractions obtained from Passiflora actinia induced catalepsy in mice. Apparently, the active principles responsible for catalepsy are present in all of the fractions of the extract.