Mucin O-glycosylating enzyme GALNT2 facilitates the malignant character of glioma by activating the EGFR/PI3K/Akt/mTOR axis

N-Acetylgalactosaminyltransferase 2 (GALNT2), the enzyme that regulates the initial step of mucin O-glycosylation, has been reported to play a role in influencing the malignancy of various cancers. However, the mechanism through which it influences gliomas is still unknown. In the current study, the Cox proportional hazards model was used to select genes. Data obtained from The Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) of clinical specimens showed that increased GALNT2 expression levels were associated with an unfavorable prognosis and a higher tumor grade in human gliomas. Then, GALNT2 knockdown and overexpression were performed in glioma cell lines and verified by qRT-PCR and western blotting. Functional assays demonstrated that GALNT2 was closely related to glioma cell proliferation, cycle transition, migration and invasion. Western blot analysis and lectin pull-down assays indicated that GALNT2 knockdown decreased the level of phosphorylated epidermal growth factor receptor (EGFR) and the expression of the Tn antigen on EGFR and affected the expression levels of p21, CDK4, cyclinD1, MMP2 and MMP9 through the EGFR/PI3K/Akt/mTOR pathway. GALNT2 overexpression had the opposite effects. In vivo, the growth of orthotopic glioma xenografts in nude mice was distinctly inhibited by the expression of GALNT2 shRNA, and the tumors with GALNT2 shRNA exhibited less aggressiveness and reduced expression of Ki67 and MMP2. Overall, GALNT2 facilitates the malignan...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research

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ConclusionsEGFR CN gain may be associated with inferior outcomes in young adults with newly diagnosed,IDH-WT GBM, suggesting a potential role for targeting EGFR in this population.
Source: Journal of Neuro-Oncology - Category: Cancer & Oncology 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
Conclusions: These data indicate that ITGB5 can serve as a predictive biomarker for GBM patient survival and is a potential therapeutic target in GBM treatment.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions: The risk signature may contribute to GBM diagnosis in future clinical practice. PMID: 31531345 [PubMed - in process]
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int 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
Examining 3D virtual reality (VR) models during presurgical planning for robotic-assisted...Read more on AuntMinnie.comRelated Reading: AR offers 3D image guidance for interventional procedures 4 practical applications of VR, AR in radiology VR, AR elevate radiologists' value in future of medicine Virtual reality may help plan, guide glioma resection Virtual reality, 3D printing resolve obscure lung cancer
Source: AuntMinnie.com Headlines - Category: Radiology Source Type: news
Publication date: Available online 17 September 2019Source: Biosensors and BioelectronicsAuthor(s): Sanaz Asgarifar, Ana L.G. Mestre, Rute C. Félix, Pedro M.C. Inácio, Maria L.S. Cristiano, Maria C.R. Medeiros, Inês M. Araújo, Deborah M. Power, Henrique L. GomesAbstractHerein, we describe an electrophysiological based sensor that reproducibly monitors and quantifies in real-time collective migration and the formation of cell-cell junctions by C6 glioma cells seeded on top of electrodes. The signal amplitude and frequency generated by the migrating cells changed over time and these parameters were...
Source: Biosensors and Bioelectronics - Category: Biotechnology 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 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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