Dataset Information

Glioma Proteome explored by LC/MS/MS

ABSTRACT: Gliomas are the most frequent and aggressive malignancies of the central nervous system. Gliomas accumulate genetic alterations that cilminate in enhanced activity of receptor tyrosine kinasesand downstream mediators. The genetic alterations (gene amplification/loss) are well characterised, little information is available regarding the changes in the proteome of gliomas of different grades. Therefore, an unbiased quantitative proteomics approach of human gliomas has been undertaken. The proteomics results indicate various up- and downregulation of pathways, in particular downregulation of the endocytic machinery components involved in initiation, formation, and scission of endocytic carriers. Both clathrin-dependent and -independent endocytosis were changed. The reduction of endocytic machinery components causes increased receptor cell surface levels, a prominent phenotype of defective endocytosis. The impaired endocytosis creates a selective advantage in glioma tumour progression due to prolonged receptor tyrosine signalling from the cell surface.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain, Brain White Matter

SUBMITTER: Paul Jenö

LAB HEAD: Paul Jenoe

PROVIDER: PXD014606 | Pride | 2019-07-23

REPOSITORIES: Pride

ACCESS DATA

Publications

Quantitative proteomics reveals reduction of endocytic machinery components in gliomas.

Buser Dominik P DP Ritz Marie-Françoise MF Moes Suzette S Tostado Cristobal C Frank Stephan S Spiess Martin M Mariani Luigi L Jenö Paul P Boulay Jean-Louis JL Hutter Gregor G

EBioMedicine 20190719

<h4>Background</h4>Gliomas are the most frequent and aggressive malignancies of the central nervous system. Decades of molecular analyses have demonstrated that gliomas accumulate genetic alterations that culminate in enhanced activity of receptor tyrosine kinases and downstream mediators. While the genetic alterations, like gene amplification or loss, have been well characterized, little information exists about changes in the proteome of gliomas of different grades.<h4>Methods</h4>We performed ...[more]

PMID: 31331834

Similar Datasets

Project description:Background: Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer in the adult population. Late diagnosis, resistance to therapeutics and recurrence of metastatic lesions account for the highest mortality rate among kidney cancer patients. Identifying novel biomarkers for early cancer detection and elucidating the mechanisms underlying ccRCC growth and progression will provide clues to treat this aggressive malignant tumor. Method: Expression studies of RING ligase praja2 and tyrosine kinase receptors (RTKs) in renal cell carcinoma was evaluated by immunoblot and immunohistochemistry. Gene transcription profiling in RCC cells was evaluated by RNA sequencing and Ingenuity Pathway Analysis. Imunofluorescence assays were used to evaluate the intracellular distribution and clearance of membrane receptors in cells devoid of praja2. Ubiquitin modifications and protein-protein interaction networks were monitored by IP, western blot, mass spectrometry and proteomic analysis. Experiments in vitro and in vivo were performed to define the role of praja2 in RTKs turnover, metabolism, renal cell carcinoma growth and metastatic diffusion. Results: We report here that the ubiquitin ligase praja2 controls endocytosis and the signal strength of different types of receptors (EGFR, VEGFR, TfR). Praja2 forms a complex with- and ubiquitinates the adaptor protein AP2m required for the activity of ATPase and acidification of endosomes and lysosomes necessary for receptor endocytosis and clearance. Downregulation of praja2 blocks the endocytosis of several membrane receptors, including EGFR, VEGFR and TfR and amplifies mitogenic and proliferative signaling as shown in the clear cell renal cell carcinoma (ccRCC). Restoring praja2 expression in RCC cells reduces EGFR levels, rewires cancer cell metabolism and inhibits growth and metastatic diffusion. In vivo, praja2 knockout mice show upregulation of tyrosine kinase receptors (RTKs) and pronounced histopathological renal alterations. Conclusion: Our findings identify praja2 as an important regulator of tyrosine kinase receptor(s) turnover and can be considered a bona fide oncosuppressor because it finely regulates signaling of several types of receptors and its loss supports kidney cancer growth and diffusion.

Project description:The significance of borderline changes (BL) in kidney allograft biopsies is widely debated. We examined differences in gene expression patterns between early clinical biopsy tissue and 3-month protocol biopsy tissue, all of which had histological BL changes and identified specific molecular BL patterns associated with poor graft outcome. The expression profiles were analyzed in training set of patients and next data were validated in validation cohort using RT-qPCR. Using the Illumina microarray technology, we observed greater expression of immunity- and inflammation-related genes in tissues from early clinical biopsies compared to 3-month protocol biopsies with BL findings. In tissues with early clinically manifested BL changes, graft deterioration within 24 months due to chronic rejection was associated with increased activation of immune, defense, and inflammatory processes, specifically with higher donor age and expression of macrophage receptor CLEC5A. In the 3-month protocol biopsies with BL changes, graft dysfunction was associated with increased expression of fibrinogen complex transcripts. This study highlights the molecular differences between clinical and subclinical biopsies with similar histological findings. The data also support a recommendation for frequent patient monitoring, especially in those who received grafts from expanded criteria donors (ECDs). The experiments were performed with total RNA derived from the renal graft biopsy samples of 28 different patients who had undergone a kidney transplantation. Only the patients with diagnosis of borderline changes early (M-bM-^IM-$2 months) or protocolar (3 months) were included in the study. RNA profiles of patients with stable and deteriorated graft function during 2 years after transplantation were compared. As microarray platform, Illumina HumanHT-12 v4.0 Expression BeadChips (Illumina) was used. The chip scanning was performed with a BeadStation 500 instrument (Illumina Inc), and the raw data were extracted with the BeadStudio Data Analysis Software (Illumina). The R software lumi package was used to further process the raw data. The quantile method was used for normalization.

Dataset Information

Glioma Proteome explored by LC/MS/MS

Publications

Quantitative proteomics reveals reduction of endocytic machinery components in gliomas.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure