Glioblastoma multiforme is an aggressive and incurable type of brain tumor. A subset of undifferentiated glioblastoma cells, known as glioblastoma tumor initiating cells (GTICs), has an essential role in the malignancy of this disease and also appears to mediate resistance to radiation therapy and chemotherapy. GTICs retain the ability to differentiate into cells with reduced malignant potential, but the signaling pathways controlling differentiation are not fully understood at this time. PTEN loss is a very common in glioblastoma multiforme and leads to aberrant activation of the phosphoinositide 3-kinase pathway. Increased signalling through this pathway leads to activation of multiple protein kinases, including atypical protein kinase C. In Drosophila, active atypical protein kinase C has been shown to promote the self-renewal of neuroblasts, inhibiting their differentiation along a neuronal lineage. This effect is mediated by atypical protein kinase c-mediated phosphorylation and inactivation of Lgl, a protein that was first characterized as a tumour suppressor in Drosophila. The effects of the atypical protein kinase C/Lgl pathway on the differentiation status of GTICs, and its potential link to PTEN loss, have not been assessed previously. Here we show that PTEN loss leads to the phosphorylation and inactivation of Lgl by atypical protein kinase C in glioblastoma cells. Re-expression of PTEN in GTICs promoted their differentiation along a neuronal lineage. This effect was also seen when atypical protein kinase C was knocked down using RNA interference, and when a non-phosphorylatable, constitutively active form of Lgl was expressed in GTICs. Thus PTEN loss, acting via atypical protein kinase C activation and Lgl inactivation, helps to maintain GTICs in an undifferentiated state.
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http://dx.doi.org/10.18632/oncotarget.1164 | DOI Listing |
Cell Mol Neurobiol
December 2024
Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
It is difficult to distinguish Parkinson's disease (PD) in the early stage from those of various disorders including atypical Parkinson's syndrome (APS), vascular parkinsonism (VP), and even essential tremor (ET), because of the overlap of symptoms. Other, more challenging problems will arise when Parkinson's disease develops into Parkinson's disease dementia (PDD) in the middle and late stages. At this time, the differential diagnosis of PDD and DLB becomes thorny.
View Article and Find Full Text PDFNeurol Int
December 2024
Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy.
: Paraneoplastic neurological syndromes (PNSs) are rare conditions characterized by immune-mediated pathogenesis, frequently associated with the presence of a neoplasm. Although a single antineuronal antibody mediates a specific syndrome, atypical manifestations mediated by the same antibody have been described. : The aim of this study was to report on an atypical case of PNS with dual positivity for anti-GAD65 and anti-CRMP5/CV2 antibodies, simultaneously characterized by cognitive decline associated with progressive ataxia and parkinsonism.
View Article and Find Full Text PDFInt J Womens Health
December 2024
Department of Gynecologic Oncology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, People's Republic of China.
Background: Epithelial ovarian cancer (EOC) remains an unmet medical challenge due to its insidious onset, atypical symptoms, and increasing resistance to conventional chemotherapeutic agents. It is imperative to explore novel biomarkers and generate innovative target drugs.
Methods: To identify potential proteins with causal association to EOC subtypes, we conducted a Mendelian Randomization (MR) analysis using 15,419 protein quantitative trait loci (pQTLs) associated with 2015 proteins.
NMR Biomed
February 2025
Department of Radiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
Asymmetry is a natural characteristic of Parkinson's disease (PD), which can be used to distinguish PD from atypical parkinsonism. Chemical exchange saturation transfer (CEST) has demonstrated value in reflecting the subtle changes related to neuron loss and abnormal protein accumulation in PD but has not been used to investigate asymmetry in PD. This study aimed to examine asymmetrical changes in the mesencephalic nucleus of PD patients with motor asymmetry using four-pool CEST analysis and to explore the relationship between imaging asymmetry and motor asymmetry.
View Article and Find Full Text PDFJ Cell Biol
March 2025
Université Paris Cité, CNRS, Institut Jacques Monod , Paris, France.
At the end of cell division, the nuclear envelope reassembles around the decondensing chromosomes. Female meiosis culminates in two consecutive cell divisions of the oocyte, meiosis I and II, which are separated by a brief transition phase known as interkinesis. Due to the absence of chromosome decondensation and the suppression of genome replication during interkinesis, it has been widely assumed that the nuclear envelope does not reassemble between meiosis I and II.
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