ORCID Profile
0000-0002-5995-6555
Current Organisation
University of Tübingen
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Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.EJCA.2011.09.006
Abstract: Glioblastoma multiforme (GBM) is a highly invasive and aggressive primary brain tumour in which loss of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), a negative regulator of PI3K signalling, is a common feature. PTEN/PI3K/Akt signalling is involved in the regulation of proliferation, apoptosis and cell migration. Deregulation of PI3K signalling is considered an essential driver in gliomagenesis. However, the role of different PI3K isoforms in glioma is still largely unclear. Here we show that the catalytic PI3K isoform p110δ is consistently expressed at a high level in various glioma cell lines. We used small interfering RNA to selectively deplete p110δ and to determine its tumourigenic roles in PTEN-deficient cells. Interestingly, knockdown of p110δ decreased the cell migration and invasion ability of all GBM cell lines tested. Mechanistically, p110δ knockdown reduced the protein levels of focal adhesion kinase and cell ision cycle 42, key regulators of cellular migration. In contrast, pharmacologic inhibition of p110δ by IC87114 or CAL-101 also clearly impaired glioma cell migration but had no obvious effect on the invasion capacity thus pinpointing to possible kinase-dependent and -independent roles of p110δ in glioma pathology. In summary, our data provide novel evidence that in glioma cells p110δ is a key regulator of cell movement and thus may contribute to the highly invasive phenotype of GBM. Isoform specific targeting of PI3Kδ may be beneficial in the treatment of glioblastoma multiforme by specifically inhibiting tumour cell migration capacity.
Publisher: Springer Science and Business Media LLC
Date: 06-12-2019
DOI: 10.1007/S00109-019-01854-1
Abstract: Pertussis toxin (PTX) is a potent virulence factor in patients suffering from whooping cough, but in its detoxified version, it is applied for vaccination. It is thought to contribute to the pathology of the disease including various CNS malfunctions. Based on its enzymatic activity, PTX disrupts GPCR-dependent signaling by modifying the α-subunit of heterotrimeric G
Publisher: Springer Science and Business Media LLC
Date: 08-09-2022
DOI: 10.1007/S11307-022-01764-8
Abstract: Cerebral hypoperfusion and vascular dysfunction are closely related to common risk factors for ischemic stroke such as hypertension, dyslipidemia, diabetes, and smoking. The role of inhibitory G protein-dependent receptor (G i PCR) signaling in regulating cerebrovascular functions remains largely elusive. We examined the importance of G i PCR signaling in cerebral blood flow (CBF) and its stability after sudden interruption using various in vivo high-resolution magnetic resonance imaging techniques. To this end, we induced a functional knockout of G i PCR signaling in the brain vasculature by injection of pertussis toxin (PTX). Our results show that PTX induced global brain hypoperfusion and microvascular collapse. When PTX-pretreated animals underwent transient unilateral occlusion of one common carotid artery, CBF was disrupted in the ipsilateral hemisphere resulting in the collapse of the cortically penetrating microvessels. In addition, pronounced stroke features in the affected brain regions appeared in both MRI and histological examination. Our findings suggest an impact of cerebrovascular G i PCR signaling in the maintenance of CBF, which may be useful for novel pharmacotherapeutic approaches to prevent and treat cerebrovascular dysfunction and stroke.
No related grants have been discovered for Bernd Nürnberg.