Dynamic response of EGF stimulation in lung cancer cells
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ABSTRACT:
PROVIDER: PRJNA328014 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The analysis of microarray time series promises a deeper insight into the dynamics of the cellular response following stimulation. A common observation in this type of data is that some genes respond with quick, transient dynamics, while other genes change their expression slowly over time. The existing methods for the detection of significant expression dynamics often fail when the expression dynamics show a large heterogeneity, and often cannot cope with irregular and sparse measurements.
2016-11-18 | GSE84095 | GEO
Project description:The analysis of microarray time series promises a deeper insight into the dynamics of the cellular response following stimulation. A common observation in this type of data is that some genes respond with quick, transient dynamics, while other genes change their expression slowly over time. The existing methods for the detection of significant expression dynamics often fail when the expression dynamics show a large heterogeneity, and often cannot cope with irregular and sparse measurements.
2016-11-18 | GSE84094 | GEO
Project description:Mutations in the epidermal growth factor receptor (EGFR) kinase domain occur in 10-30% of lung adenocarcinoma. Leucine to arginine substitution at amino acid position 858 (L858R) accounts for around 50% of EGFR-tyrosine kinase inhibitor (TKI) sensitizing mutations. A second site mutation in the gatekeeper residue (T790M) accounts for around 60% of acquired resistance to EGFR-TKIs. We sought to identify the immediate direct and indirect targets of these mutant EGFRs in lung adenocarcinoma and their modulation by erlotinib, the first generation, and most widely used EGFR-directed TKI. We undertook stable isotope labeling of amino acids in cell culture (SILAC), phosphopeptide enrichment, and quantitative mass spectrometry to identify dynamic changes of phosphorylation downstream of mutant EGFRs in lung adenocarcinoma cells harboring L858R or L858R/T790M mutations and their modulation by erlotinib inhibition. Phosphorylation at the majority of phosphosites identified exhibited no change upon either EGF stimulation or erlotinib inhibition. Only around 7% of phosphosites identified and quantified showed increased phosphorylation upon EGF stimulation in either cell line. However, while phosphorylation at 61% of these phosphosites decreased upon erlotinib inhibition in the TKI sensitive H3255 cells, only 24% of such sites exhibited decreased phosphorylation upon erlotinib inhibition in the TKI resistant H1975 cells. Top canonical pathways that were inhibited upon erlotinib treatment in sensitive cells, but not the resistant cells include EGFR, Insulin receptor, HGF, MAPK, mTOR, p70S6K and JAK/STAT signaling. We identified phosphosites in proteins of the autophagy network, such as ULK1 (S623) that is constitutive phosphorylated in these lung adenocarcinoma cells, but phosphorylation is inhibited upon erlotinib treatment in sensitive cells, but not resistant cells. Finally, kinase-substrate prediction analysis from our data indicated that substrates of basophilic kinase families, AGC, CAMK and STE were significantly enriched and those of proline directed kinase families, CMGC and CK were significantly depleted among substrates that exhibit increased phosphorylation upon EGF stimulation and reduced phosphorylation upon TKI inhibition. This is the first study to date to examine global phosphorylation changes upon erlotinib treatment of lung adenocarcinoma cells and results from this study provide new insights into signaling downstream of mutant EGFRs in lung adenocarcinoma.
2015-01-30 | PXD001101 | Pride
Project description:Analysis of cysteine redox networks 0, 2, 5, 15, 30, and 60 minutes after stimulation with EGF in A431 cells using a new workflow 'OxRAC' optimized to assess dynamic redox regulation.
2020-01-10 | PXD010880 | Pride
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-11-18 | GSE84096 | GEO
Project description:ELK1 is a well-known target of the ERK branch (EGF-responsive) of the MAP kinase pathway. This transcription profiling experiment studied the effects of ELK1 depletion by siRNA and subsequent EGF stimulation.
2012-07-20 | E-MEXP-3407 | biostudies-arrayexpress
Project description:Triplex stable isotope dimethyl labeling of phosphotyrosine peptides after EGF stimulation
2010-07-09 | PRD000124 | Pride
Project description:In addition to supporting increased cellular metabolism for untethered neoplastic growth, recent reports have indicated that certain metabolic enzymes may exhibit alternative functions in human cancers. Despite the ability to import serine from the microenvironment, lung tumors significantly elevate expression of biosynthetic enzymes responsible for the de novo production of serine, notably phosphoserine aminotransferase 1 (PSAT1). Highlighting the relevance of PSAT1 in lung cancer, patients with increased expression demonstrated poorer overall survival, so characterizing its role in lung tumor progression may ultimately identify different therapeutic strategies targeting this disease. Our preliminary studies now demonstrate a potential alternative function, beyond serine synthesis, of PSAT1 in lung tumor cells. Specifically, we found that PSAT1 localizes to the nucleus upon epidermal growth factor stimulation [via activating EGFR mutation (PC9, inhibited by the EGFR-mutant specific inhibitor, Erlotinib) or EGF stimulation (A549, EGFR-WT)] and regulates the nuclear import of pyruvate kinase M2 (PKM2). Importantly, nuclear PKM2 has been demonstrated to directly phosphorylate histones and modify gene transcription. In further support of this functional interaction, within yeast, PKM2 association with serine synthetic enzymes resulted in pervasive chromatin remodeling and alteration in global gene expression. Therefore, our objective in this proposal is to define gene signatures promoted by PSAT1-mediated nuclear PKM2 translocation in response to EGF-signaling in human lung cancer cells.
2024-04-23 | GSE173270 | GEO
Project description:Using basal‐like untransformed cells, MCF10A, as a model system, data from our laboratory showed that both mRNAs and microRNAs exhibit dynamic changes in expression following EGF stimulation (Amit et al, 2007; Avraham et al, 2010; Kostler et al, 2013). We further demonstrated that the inducible mRNAs and microRNAs are embedded into regulatory subnetworks, which are deregulated in diverse tumor types. Considering the emerging roles for long noncoding RNAs (lncRNAs) in metastasis of breast cancer (Serviss et al, 2014), we raised the possibility that some EGF‐inducible lncRNAs might play a role in basal‐like breast cancer. Thus, MCF10A cells were stimulated with EGF (10 ng/ml) for 0, 20, 40, 60, 120, 240 and 480 minutes. RNA was then extracted from cells and expression of lncRNAs was measured using Agilent SurePrint microarrays.
2017-07-27 | E-MTAB-4822 | biostudies-arrayexpress
Project description:Expression data from ERBB2 over-expression and EGF stimulation in MCF10A cells The cells were transduced with retroviruses encoding vector control (pBabe) or pBabe-ErbB2. After infection cells were switched to assay medium supplemented with only 2% horse serum and no EGF. For EGF stimulation, cells transduced with empty vector were treated with EGF at 50 ng/ml for 2 hours before harvesting.
2010-02-21 | E-GEOD-14987 | biostudies-arrayexpress