RhoA regulates translation of the Nogo-A decoy SPARC in white matter-invading glioblastomas

This study demonstrates that the prevalent activation of AKT in gliomas increases the ER protein-folding capacity and enables tumor cells to utilize a side effect of RhoA activation: the perturbation of the IRE1 α-mediated decay of SPARC mRNA. Once translation is initiated, glioblastoma cells rapidly secrete SPARC to block Nogo-A from inhibiting migration via RhoA. By advanced ultramicroscopy for studying single-cell invasion in whole, undissected mouse brains, we show that gliomas require SPARC for invadi ng into white matter structures. SPARC depletion reduces tumor dissemination that significantly prolongs survival and improves response to cytostatic therapy. Our finding of a novel RhoA-IRE1 axis provides a druggable target for interfering with SPARC production and underscores its therapeutic value .
Source: Acta Neuropathologica - Category: Neurology Source Type: research

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ConclusionOur case shows that diffuse midline glioma is a CNS tumor not limited to young population but occurring also in middle aged patients with an insidious pattern. We therefore recommend to perform biopsy at very early stages in patients with atypical brainstem lesions.
Source: Journal of Clinical Neuroscience - Category: Neuroscience Source Type: research
Authors: Vienne-Jumeau A, Tafani C, Ricard D Abstract Adult primary tumors of the central nervous system are rare, but the incidence is increased in some European countries. Several environmental exposures have been investigated as potential risk factors, but for most, scientific evidence is still lacking. Here we review studies of environmental factors potentially involved in the carcinogenesis of brain tumors: the potential association between primary central nervous system tumors and ionizing radiation, some toxic agents (N-nitroso compounds, pesticides), air pollution, and radiofrequency electromagnetic waves. ...
Source: Revue Neurologique - Category: Neurology Tags: Rev Neurol (Paris) Source Type: research
Contributors : Guan Ying ; Chen Die ; Zhan Yuefu ; Chen JianqiangSeries Type : Expression profiling by high throughput sequencingOrganism : Rattus norvegicusGliomas is the most common and aggressive primary brain tumor. The C6 glioma cell line has been widely used for decades as experimental model system for the study of glioblastoma growth and invasion. Recently, aquaporin-1 (Aqp1) is reported to facilitate cell migration and potentially involved in tumor progression. Here we overexpressed Aqp1 in C6 cells to examine its potential role in glioblastoma. We found overexpression of Aqp1 in C6 cells significantly increased ce...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Rattus norvegicus Source Type: research
Publication date: Available online 18 September 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Fangfang Li, Zongliang Liu, Heyuan Sun, Chunmei Li, Wenyan Wang, Liang Ye, Chunhong Yan, Jingwei Tian, Hongbo WangAbstractGliomas are the most common primary intracranial neoplasms among all brain malignancies, and the microtubule affinity regulating kinases (MARKs) have become potential drug targets for glioma. Here, we report a novel dual small-molecule inhibitor of MARK3 and MARK4, designated as PCC0208017. In vitro, PCC0208017 strongly inhibited kinase activity against MARK3 and MARK4, and strongly reduced proliferation in...
Source: Acta Pharmaceutica Sinica B - Category: Cancer & Oncology Source Type: research
Publication date: December 2019Source: Biomedicine &Pharmacotherapy, Volume 120Author(s): Fan Feng, Moxuan Zhang, Chuanchao Yang, Xueyuan Heng, Xiujie WuAbstractAutophagy, a self-digestion intracellular catabolic process, plays a crucial role in cellular homeostasis under conditions of starvation, oxidative stress and genotoxic stress. The capability of maintaining homeostasis contributes to preventing malignant behavior in normal cells. Many studies have provided compelling evidence that autophagy is involved in brain tumor recurrence and chemotherapy and radiotherapy resistance. Gliomas, as the primary central nervou...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
Publication date: 17 September 2019Source: Cell Reports, Volume 28, Issue 12Author(s): Erik R. Abels, Sybren L.N. Maas, Lisa Nieland, Zhiyun Wei, Pike See Cheah, Eric Tai, Christy-Joy Kolsteeg, Sophie A. Dusoswa, David T. Ting, Suzanne Hickman, Joseph El Khoury, Anna M. Krichevsky, Marike L.D. Broekman, Xandra O. BreakefieldSummaryGliomas are primary, diffusely infiltrating brain tumors. Microglia are innate immune cells in the CNS and make up a substantial portion of the tumor mass. Glioma cells shape their microenvironment, communicating with and reprogramming surrounding cells, resulting in enhanced angiogenesis, immune...
Source: Cell Reports - Category: Cytology Source Type: research
When glioma results are inconclusive on MRI, clinicians should consider fluoroethyl-tyrosine...Read more on AuntMinnie.comRelated Reading: How cost-effective is intraoperative MRI for gliomas? FET-PET adds 'relevant' info to pediatric cancer cases FLT-PET points toward survival for glioblastoma patients SNMMI: FET-PET could have answers for brainstem glioma SNMMI: FET-PET aids pediatric brain cancer patients
Source: AuntMinnie.com Headlines - Category: Radiology Source Type: news
In conclusion, although the CNS is not any more considered as an "immunological sanctuary" and despite some encouraging experimental and clinical results in CNS oncotherapy, the routine application of IT in case of MGs is still awaited. PMID: 31533142 [PubMed - in process]
Source: Magyar Onkologia - Category: Cancer & Oncology Authors: Tags: Magy Onkol Source Type: research
In cancer cells, aberrant DNA methylation is commonly associated with transcriptional alterations, including silencing of tumor suppressor genes. However, multiple epigenetic mechanisms, including polycomb repressive marks, contribute to gene deregulation in cancer. To dissect the relative contribution of DNA methylation–dependent and –independent mechanisms to transcriptional alterations at CpG island/promoter-associated genes in cancer, we studied 70 samples of adult glioma, a widespread type of brain tumor, classified according to their isocitrate dehydrogenase (IDH1) mutation status. We found that most tran...
Source: Genome Research - Category: Genetics & Stem Cells Authors: Tags: RESEARCH Source Type: research
ily Andrei M. Mikheev Diffuse invasion into adjacent brain matter by glioblastoma (GBM) is largely responsible for their dismal prognosis. Previously, we showed that the TWIST1 (TW) bHLH transcription factor and its regulated gene periostin (POSTN) promote invasive phenotypes of GBM cells. Since TW functional effects are regulated by phosphorylation and dimerization, we investigated how phosphorylation of serine 68 in TW regulates TW dimerization, POSTN expression, and invasion in glioma cells. Compared with wild-type TW, the hypophosphorylation mutant, TW(S68A), impaired TW heterodimerization with the E12 bHLH trans...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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