Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA267510 | ENA |
REPOSITORIES: ENA
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Project description:mathematical model, with accompanying quantitative experimental data, for binding and trafficking properties of the epidermal growth factor (EGF) receptor on B82 fibroblasts, and propose a theoretical dependence of cell proliferation rate on these properties. Model encoded by Matthieu Maire adn submitted to BioModels by Krishna Kumar Tiwari.
2020-03-19 | MODEL2003190005 | BioModels
Project description:Long non-coding RNAs (lncRNAs) emerge as new regulators of various cell activities. The G1 to S phase (G1/S) transition is the key step that drives cell to the division cycle, and its dysregulation contributes to unrestrained cell proliferation and consequent tumor development.In this study, we examined lncRNA expression profiles during cell cycle using serum starvation-stimulation model in human skin fibroblasts (SFs) and identified that lncRNA SnoRNA Host Gene 17 (SNHG17) was elevated at the early G1 phase and in hepatocellular carcinoma (HCC) tissues. Both gain- and loss-of function studies disclosed that SNHG17 increased c-Myc protein level, accelerated G1/S transition and cell proliferation, and consequently promoted tumor growth. Up-regulation of SNHG17 was correlated with high c-Myc level in human HCC. Mechanistically, the 1-150-nt of SNHG17 physically interacted with the 1035-1369-aa of leucine rich pentatricopeptide repeat containing (LRPPRC) protein, and disrupting this interaction abrogated the promoting role of SNHG17 in c-Myc up-regulation, G1/S transition and cell proliferation. And the proliferation-stimulatory effect of SNHG17 was abrogated by silencing c-Myc or LRPPRC. Furthermore, silencing SNHG17 or LRPPRC increased the ubiquitylated c-Myc level and reduced c-Myc stability, suggesting that SNHG17 may inhibit c-Myc ubiquitination and thus enhance c-Myc level and facilitate proliferation by interacting with LRPPRC. Our findings identify a novel SNHG17-LRPPRC-c-Myc regulatory axis and elucidate its roles in G1/S transition and tumor growth, which provide potential targets for cancer therapy.
2021-02-10 | GSE166448 | GEO
Project description:The purpose of this study was to assess the preliminary antitumor activity, safety and tolerability of tepotinib in combination with cetuximab in participants with RAS/BRAF wild-type left-sided Metastatic Colorectal Cancer (mCRC) having acquired resistance to anti-epidermal growth factor receptor (EGFR) antibody targeted therapy due to mesenchymal epithelial transition (MET) amplification.
| 2348989 | ecrin-mdr-crc
Project description:Background: UNC50 has long been recognized as a Golgi apparatus protein in yeast, and is involved in nicotinic receptor trafficking in Caenorhabditis elegans, but little is known about UNC50 gene function in human biology despite it being conserved from yeast to high eukaryotes. Objectives: We investigated the relation between UNC50 and human hepatocellular carcinoma (HCC) and the potential mechanisms underlying HCC development. Methods: UNC50 mRNA expression patterns in 12 HCC and adjacent non-cancerous tissues determined using northern blotting were confirmed by real-time PCR in another 44 paired tissues. Microarray experiments were used to screen for global effects of UNC50 knockdown in the Hep3B cell line, and were confirmed by real-time PCR, western blotting, flow cytometry, and tetrazolium assay in both UNC50 overexpression and knockdown Hep3B cells. Results: UNC50 expression levels were upregulated in HCC tissues in comparison with the adjacent non-cancerous tissues. UNC50 knockdown reduced mRNA levels of the downstream targets of the epidermal growth factor receptor (EGFR) pathway: cyclin D1 (CCND1), EGF, matrix metalloproteinase-7 (MMP7), aldose reductase-like 1 (AKR1B10), cell surfaceM-bM-^@M-^Sassociated mucin 1 (MUC1), and gastrin (GAST). Moreover, UNC50 influenced EGF, inducing cell cycle entry by affecting cell surface EGFR amounts. Conclusions: UNC50 is a potential oncogene that promotes HCC progression by affecting the EGFR pathway. To gain insight into the role UNC50 plays in HCC progression, we used microarray analyses to identify indirect evidence of UNC50 gene function via the knockdown strategy in Hep3B cells. Hep3B cells transfected with the shRNA expression plasmids shR-467, shR-554, shR-749, and shR-MOCK were purified with 1ug/ml puromycin, and the total RNA from each cell was extracted and analyzed with oligo microarrays.
2014-11-17 | E-GEOD-63322 | biostudies-arrayexpress
Project description:Background: UNC50 has long been recognized as a Golgi apparatus protein in yeast, and is involved in nicotinic receptor trafficking in Caenorhabditis elegans, but little is known about UNC50 gene function in human biology despite it being conserved from yeast to high eukaryotes. Objectives: We investigated the relation between UNC50 and human hepatocellular carcinoma (HCC) and the potential mechanisms underlying HCC development. Methods: UNC50 mRNA expression patterns in 12 HCC and adjacent non-cancerous tissues determined using northern blotting were confirmed by real-time PCR in another 44 paired tissues. Microarray experiments were used to screen for global effects of UNC50 knockdown in the Hep3B cell line, and were confirmed by real-time PCR, western blotting, flow cytometry, and tetrazolium assay in both UNC50 overexpression and knockdown Hep3B cells. Results: UNC50 expression levels were upregulated in HCC tissues in comparison with the adjacent non-cancerous tissues. UNC50 knockdown reduced mRNA levels of the downstream targets of the epidermal growth factor receptor (EGFR) pathway: cyclin D1 (CCND1), EGF, matrix metalloproteinase-7 (MMP7), aldose reductase-like 1 (AKR1B10), cell surface–associated mucin 1 (MUC1), and gastrin (GAST). Moreover, UNC50 influenced EGF, inducing cell cycle entry by affecting cell surface EGFR amounts. Conclusions: UNC50 is a potential oncogene that promotes HCC progression by affecting the EGFR pathway.
2014-11-17 | GSE63322 | GEO
Project description:Using a kinome-centred CRISPR/Cas9 genetic screen, we identify here that inhibition of the epidermal growth factor receptor (EGFR) is synthetic lethal with lenvatinib in liver cancer cells. We found that the combination of the EGFR inhibitor gefitinib and lenvatinib displays potent anti-proliferative effect in HCC cell lines that express EGFR in vitro and of xenografted HCC cell lines or patient-derived HCC tumours in mice. Herre, we analyzed the different transcriptome profiling of HCC cells treated with DMSO, lenvatinib, gefitinib, and lenvatinib plus gefitinib by RNA-sequencing.
2021-07-22 | GSE157905 | GEO
Project description:Overexpression of human epidermal growth factor receptor 2 (HER-2) occurs in 20% of all breast cancer subtypes, those that present the worst prognostic outcome through a very invasive and aggressive tumour. HCC-1954 (HER-2+) is a highly invasive, metastatic cell line whereas MCF-7 is mildly aggressive and non-invasive. We investigated membrane proteins from both cell lines that could have a pivotal biological significance in the metastatic process. Membrane protein enrichment for HCC-1954 and MCF-7 proteomic analysis was performed. The samples were analysed on a two-dimensional liquid chromatography coupled to mass spectrometry (2-D-SCX/RP-LCMS system) and the protein expression was quantified by MSE method. High abundance membrane proteins were confirmed by western blot, immunofluorescence, and flow cytometry. Protein interaction prediction and correlations with TCGA patient’s data were conducted by bioinformatic analysis. The comparison between HCC-1954 and MCF-7 membrane proteins revealed that proteins involved in cytoskeleton organization, such as HER-2, β-1 integrin, E-cadherin and CD166 (ALCAM) were more abundant in HCC-1954. The Cancer Genome Atlas (TCGA) analysis showed a trend toward a positive correlation between HER-2 and β-1 integrin in HER-2+ breast cancer patients. Differences in protein profile and abundance reflect distinctive capabilities for motility and invasiveness between cell lines. HCC-1954 could be an excellent model to study β1 integrin and epithelial–mesenchymal transition (EMT) involvement in trastuzumab resistance mechanisms.
2022-10-14 | PXD023876 | Pride
Project description:Ligand-stimulated epidermal growth factor receptor (EGFR) signaling plays fundamental roles in normal cell physiology, such as cell growth, cell proliferation, and cell survival. Deregulation of EGFR signaling contributes to the development and progression of diseases including cancer. Despite its essential role in biology, the mechanisms by which EGFR signaling is regulated in cells are still poorly understood. Here, we demonstrate that O-linked N-acetyl-glucosamine (O-GlcNAc) modification serves as an important regulator of EGFR intracellular trafficking and degradation. Mechanistically, O-GlcNAcylation of hepatocyte growth factor regulated tyrosine kinase substrate (HGS), a key protein in EGFR intraluminal sorting pathway, inhibits HGS interaction with signal-transducing adaptor molecule (STAM), thereby impairing the formation of endosomal sorting complex required for transport-0 (ESCRT-0). Moreover, O-GlcNAcylation increases HGS ubiquitination and decreases its protein stability in cells. Consequently, HGS O-GlcNAcylation inhibits EGFR intraluminal sorting and lysosomal degradation, leading to the accumulation of EGFR and prolonged EGFR signaling in cells.
2022-04-04 | PXD031700 | Pride
Project description:Cholangiocyte Ciliary Defects Induce Sustained Epidermal Growth Factor Receptor Signaling
| PRJNA1157847 | ENA
Project description:Receptor tyrosine kinases (RTK) bind growth factors and are critical for cell proliferation and differentiation. Their dysregulation leads to a loss of growth control, often resulting in cancer. Epidermal growth factor receptor (EGFR) is the prototypic RTK and can bind several ligands exhibiting distinct mitogenic potentials. Whereas the phosphorylation on individual EGFR sites and their roles for downstream signaling have been extensively studied, less is known about ligand-specific ubiquitination events on EGFR, which are crucial for signal attenuation and termination. We used a proteomics-based workflow for absolute quantitation combined with mathematical modelling to unveil potentially decisive ubiquitination events on EGFR from the first 30 seconds to 15 minutes of stimulation. Four ligands were used for stimulation: epidermal growth factor (EGF), heparin-binding-EGF like growth factor, transforming growth factor- and epiregulin. Whereas only little differences in the kinetic profiles of individual ubiquitination sites were observed, the overall amount of modified receptor differed depending on the used ligand, indicating that absolute magnitude of EGFR ubiquitination, and not distinctly regulated ubiquitination sites, is a major determinant for signal attenuation and the subsequent cellular outcomes.
2022-05-31 | PXD019621 | Pride