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Multi-omics analysis of β-catenin oncogenic networks

ABSTRACT: We used interaction and expression proteomic techniques in conjunction with RNA-Seq transcriptomic analysis to analyse how a β-catenin stabilizing mutation alters molecular networks in colorectal cancer cells. Integrated computational analyses of allowed us to identify significantly altered sub-networks linked to β-catenin oncogenesis.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Colon Cancer

SUBMITTER: Rob Ewing

LAB HEAD: Rob Ewing

PROVIDER: PXD006053 | Pride | 2018-05-18

REPOSITORIES: Pride

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			Action	DRS
	Cyt_1_1_011713.raw	Raw
	Cyt_1_2_011713.raw	Raw
	Cyt_2_1_011713.raw	Raw
	Cyt_2_2_011713.raw	Raw
	Cyt_3_1_011713.raw	Raw

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Publications

Multiproteomic and Transcriptomic Analysis of Oncogenic β-Catenin Molecular Networks.

Ewing Rob M RM Song Jing J Gokulrangan Giridharan G Bai Sheldon S Bowler Emily H EH Bolton Rachel R Skipp Paul P Wang Yihua Y Wang Zhenghe Z

Journal of proteome research 20180518 6

The dysregulation of Wnt signaling is a frequent occurrence in many different cancers. Oncogenic mutations of CTNNB1/β-catenin, the key nuclear effector of canonical Wnt signaling, lead to the accumulation and stabilization of β-catenin protein with diverse effects in cancer cells. Although the transcriptional response to Wnt/β-catenin signaling activation has been widely studied, an integrated understanding of the effects of oncogenic β-catenin on molecular networks is lacking. We used affinity ...[more]

PMID: 29747501

Similar Datasets

Analysis of the β-catenin oncogenic interactome

Project description:e used interaction and expression proteomic techniques in conjunction with RNA-Seq transcriptomic analysis to analyse how a β-catenin stabilizing mutation alters molecular networks in colorectal cancer cells. Integrated computational analyses of allowed us to identify significantly altered sub-networks linked to β-catenin oncogenesis.

2018-10-05 | PXD006051 | Pride

Cross-species complementation reveals conserved functions for EARLY FLOWERING 3 between monocots and dicots.

Project description:Plant responses to the environment are shaped by the external stimuli and internal signaling pathways. In both the model plant Arabidopsis thaliana and crop species, circadian clock factors have been identified as critical for growth, flowering and circadian rhythms. Outside of A. thaliana, however, little is known about the molecular function of clock genes. Therefore, we sought to compare the function of Brachypodium distachyon and Seteria viridis orthologs of EARLY FLOWERING3, a key clock gene in A. thaliana. To identify both cycling genes and putative ELF3 functional orthologs in S. viridis, a circadian RNA-seq dataset and online query tool (Diel Explorer) was generated as community resource to explore expression profiles of Setaria genes under constant conditions after photo- or thermo-entrainment. The function of ELF3 orthologs from A. thaliana, B. distachyon, and S. viridis were tested for complementation of an elf3 mutation in A. thaliana. Despite comparably low sequence identity versus AtELF3 (< 37%), both monocot orthologs were capable of rescuing hypocotyl elongation, flowering time and arrhythmic clock phenotypes. Molecular analysis using affinity purification and mass spectrometry to compare physical interactions also found that BdELF3 and SvELF3 could be integrated into similar complexes and networks as AtELF3, including forming a composite evening complex. Thus, we find that, despite 180 million years of separation, BdELF3 and SvELF3 can functionally complement loss of ELF3 at the molecular and physiological level.

2018-01-08 | PXD006352 | Pride

BCL9 provides multi-cellular communication properties in colorectal cancer by interacting with paraspeckle proteins

Project description:Colorectal cancer (CRC) is the third most commonly diagnosed cancer, which despite recent advances in treatment, remains incurable due to molecular heterogeneity of tumor cells. The B-cell lymphoma 9 (BCL9) oncogene functions as a transcriptional co-activator of the Wnt/β-catenin pathway, which plays critical roles in CRC pathogenesis. Here we have identified a β-catenin-independent function of BCL9 in a poor-prognosis subtype of CRC tumors characterized by expression of stromal and neural associated genes. In response to spontaneous calcium transients or cellular stress, BCL9 is recruited adjacent to the interchromosomal regions, where it stabilizes the mRNA of calcium signaling and neural associated genes by interacting with paraspeckle proteins. BCL9 subsequently promotes tumor progression and remodeling of the tumor microenvironment (TME) by sustaining the calcium transients and neurotransmitter-dependent communication among CRC cells. These data provide additional insights into the role of BCL9 in tumor pathogenesis and point towards additional avenues for therapeutic intervention.

2020-05-27 | PXD016172 | Pride

Hyperactive Mouse Serotonin Transporter Interacting Proteins LC-MSMS

Project description:The serotonin (5-HT) transporter (SERT) is a key determinant of the concentration of 5-HT available for synaptic signaling and is the target of the antidepressant-selective 5-HT reuptake inhibitors (SSRIs). In addition to the role of SERT in mediating the actions of antidepressant medications, multiple, rare gain of function coding variants in SERT have been identified in subjects with autism spectrum disorder (ASD). The Blakely lab has extensively characterized the structural and functional impact of one of these variants, SERT Ala56, in vitro and in vivo, revealing a constitutively-imposed, biased conformation that enhances transporter function and that perturbs transporter regulation. We hypothesize that SERT Ala56 disrupts the interactions of molecular networks that normally ensure proper transporter structure, localization and regulation, and whose elucidation may reveal new determinants of serotonergic dysfunction in ASD. Here, we pursue an unbiased proteomic analysis of changes in SERT interacting protein (SIPs) imposed by the SERT Ala56 variant, expressed in transgenic mice. Further investigation of the SIPs and associated networks nominated through our studies may provide new opportunities to detect and modulate brain networks that contribute to the underlying complexity of ASD.

2020-05-29 | PXD018695 | Pride

Identification of phosphorylation sites on purified recombinant protein Dynamin-like protein 1

Project description:Drp1 is a GTPase involves in mitochondrial division. The phosphorylation of Drp1 is reported to influence Drp1 activity. Two well known Drp1 phosphorylation sites have been identified. In here, we in vitro phosphorylate S579 site by ERK2 kinase on WT-Drp1 or S600D-Drp1 mutant and try to identify the phosphorylation by Mass Spec.

2024-06-16 | PXD046824 | Pride

CDC14B interactome - The proteomic approach aimed at the identification of interaction partners for the human dual phosphatase and tumor suppressor CDC14B by Co-inmunoprecipitation (Co-IP) experiments. In this approach, CDC14B interactomes from unsynchronized and G2/M enriched cells were compared semi-quantitatively based on spectral counting. This approach yielded the deubiquitylase USP9X as a G2/M-specific CDC14B interactor which has been confirmed by Western-blot (WB).

Project description:The proteomic approach aimed at the identification of interaction partners for the human dual phosphatase and tumor suppressor CDC14B by Co-inmunoprecipitation (Co-IP) experiments. In this approach, CDC14B interactomes from unsynchronized and G2/M enriched cells were compared semi-quantitatively based on spectral counting. This approach yielded the deubiquitylase USP9X as a G2/M-specific CDC14B interactor which has been confirmed by Western-blot (WB).

2020-03-25 | PXD012732 | Pride

Arabidopsis SNAREs SYP121 and SYP122 mediate the secretion of distinct cargo 2 subsets

Project description:SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins drive vesicle fusion and contribute to homoeostasis, pathogen defence, cell expansion, and growth in plants. In Arabidopsis thaliana, the two homologous Qa-SNAREs, SYP121 and SYP122 facilitate the majority of secretory traffic to the plasma membrane. In the absence of stress, the single mutants are indistinguishable from wild-type plants, implying a redundancy in their functions. Nonetheless, several studies suggest differences among the secretory cargo of these SNAREs. To address this issue, we conducted an analysis of the proteins secreted by cultured wild-type, syp121 and syp122 mutant Arabidopsis seedlings. Here, we report that a number of cargo proteins are associated differentially with traffic mediated by SYP121 and SYP122. The data also point to important overlaps between the SNAREs. The findings lead us to conclude that the two Qa-SNAREs mediate distinct, but complementary secretory pathways during vegetative plant growth.

2018-09-18 | PXD009640 | Pride

Transcription profiling of mouse pancreas at embryonic days 14.5 and 16.5 from animals lacking beta-catenin, a mediator of Wnt signaling and a component of the cadherin-catenin epithelial adhesion complex

Project description:Beta-catenin is an essential mediator of canonical Wnt signaling and a central component of the cadherin-catenin epithelial adhesion complex. Dysregulation of beta-catenin expression has been described in pancreatic neoplasia. Newly published studies have suggested that beta-catenin is critical for normal pancreatic development although these reports reached somewhat different conclusions. In addition, the molecular mechanisms by which loss of beta-catenin affects pancreas development are not well understood. The goals of this study then were; 1] to further investigate the role of beta-catenin in pancreatic development using a conditional knockout approach and 2] to identify possible mechanisms by which loss of beta-catenin disrupts pancreatic development. A Pdx1-cre mouse line was used to delete a floxed beta-catenin allele specifically in the developing pancreas, and embryonic pancreata were studied by immunohistochemistry and microarray analysis. Experiment Overall Design: Parameter: embryonic pancreas from wild type and Pdx1Cre/+; beta-cateninflox/flox Experiment Overall Design: Sample type: RNA Experiment Overall Design: Source name: Embryonic day 14.6 and 16.5 pancreas Experiment Overall Design: Organism: Mus Musculus Experiment Overall Design: Strain: Derived from an intercross of Pdx1Cre/+ ; beta-cateninflox/+ mice. Experiment Overall Design: Extracted molecule:Total RNA Experiment Overall Design: In the study, we hybridized RNA from Embryonic day 14.6 and 16.5 pancreas of wild type (WT) control and Pdx1Cre/+; beta-cateninflox/floxÂ beta-catenin null in the pancreas) embryonic pancreas to Affymetrix MOE430 2.0 GeneChip® arrays containing 45,101 well characterized mouse genes/ESTs.

2007-12-13 | E-GEOD-7430 | biostudies-arrayexpress

ARP-T1 is a ciliary protein associated with a novel ciliopathy in inherited basal cell cancer, Bazex-Dupré-Christol Syndrome

Project description:The interactors of the protein Arp-T1 were studied in human cells ( keratinocytes)

2021-05-06 | PXD016557 | Pride

Human Rheumatoid Arthritis LC-MSMS

Project description:Malondialdehyde-modified epitopes (MDA-epitopes) can elicit specific autoantibody that expressed oxidative stress arising in rheumatoid arthritis (RA). The purpose of this study was to discover and validate MDA-peptide adducts as novel biomarkers using concanavalin A affinity chromatography, 1D SDS-PAGE, in-gel digestion, and label-free nano-LC-MS, and evaluate levels of serum MDA, MDA-protein adducts, proteins and autoantibody isotypes against an unmodified and MDA-peptide from Taiwanese female patients with RA and healthy controls (HCs). Levels of serum MDA and MDA-protein adducts were significantly higher in RA patients versus HCs. Four differentially expressed novel MDA-peptides were selected that relative modification ratio were 2-fold differences to examine protein levels and assess autoantibodies to MDA-peptides in RA patients compared with HCs. Four of peptides are autoantigens. Furthermore, 4 MDA-peptides can induce more autoantibody isotypes that are statistical significance in RA patients compared to HCs. Serum IgG and IgM against MDA-peptides showed excellent diagnostic performance in discriminating among RA patients and HCs: area under the curve (AUC, 0.96 ~ 0.98), sensitivity (88.9% ~ 97.8%) and specificity (88.9% ~ 100%). Autoantibodies to MDA-epitopes indicate oxidative modifications occurring in RA, and might be useful as clinical markers fro RA diagnosis if further investigated.

2021-02-25 | PXD004546 | Pride

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