Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Lapatinib action and resistance in breast cancer

ABSTRACT: We used an established cell line model of lapatinib resistance and employed explorative mass spectrometry to profile the proteome, kinome and phosphoproteome changes in an effort to systematically investigate initial inhibitor response and concomitant kinome reprogramming and signaling rewiring in resistance. Experiments were performed in three biological replicates

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Breast Cancer

SUBMITTER: Benjamin Ruprecht

LAB HEAD: Simone Lemeer

PROVIDER: PXD004981 | Pride | 2017-02-27

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	01460_A02_P014933_B00_A00_R1.raw	Raw
	01460_C01_P014927_B00_A00_R1.raw	Raw
	01460_D01_P014928_B00_A00_R1.raw	Raw
	01460_E01_P014929_B00_A00_R1.raw	Raw
	01460_F01_P014930_B00_A00_R1.raw	Raw

Items per page:

1 - 5 of 121

Similar Datasets

Lapatinib action and resistance in breast cancer

Project description:We used an established cell line model of lapatinib resistance and employed explorative mass spectrometry to profile the proteome, kinome and phosphoproteome changes in an effort to systematically investigate initial inhibitor response and concomitant kinome reprogramming and signaling rewiring in resistance. Experiments were performed in three biological replicates

2017-03-31 | MSV000080839 | MassIVE

The gut microbiota promotes hepatic fatty acid desaturation and elongation in mice

Project description:Interactions between the gut microbial ecosystem and host lipid homeostasis are highly relevant to host physiology and metabolic diseases. We present a comprehensive multi-omics view of the effect of intestinal microbial colonization on hepatic lipid metabolism, integrating transcriptomic, proteomic, phosphoproteomic, and lipidomic analyses of liver and plasma samples from germfree and specific pathogen-free mice. Microbes induced monounsaturated fatty acid generation by stearoyl-CoA desaturase 1 and polyunsaturated fatty acid elongation by fatty acid elongase 5, leading to significant alterations in glycerophospholipid acyl-chain profiles. Germfree mice contained more abundant saturated and poly-unsaturated lipids, whereas colonized mice primarily contained mono-unsaturated lipids. A composite classification score calculated from the observed alterations in fatty acid profiles in germfree mice clearly differentiated antibiotic-treated mice from untreated controls with high sensitivity. Mechanistic investigations revealed that acetate originating from gut microbial degradation of dietary fiber serves as precursor for hepatic synthesis of C16 and C18 fatty acids and their related glycerophospholipid species that are also released into the circulation.

2018-07-20 | PXD010412 | Pride

Label-Free Phosphoproteomics Profiling of Fission Yeast Schizosaccharomyces pombe

Project description:The phosphorylation of proteins modulates various functions of proteins and plays an important role in regulation of cell signaling. In the recent years, the label-free quantitative (LFQ) phos-phoproteomics has become the powerful tool to analyze the phosphorylation of proteins within the complex samples. Despite the great progress, the studies of protein phosphorylations are still limited in throughput, robustness, and reproducibility, hampering analyses that involve multiple perturbations, such as those needed to follow the dynamics of phosphoproteomes. To address these challenges, we introduce here the LFQ phosphoproteomics workflow that is based on Fe-IMAC phosphopeptide enrichment followed by strong anion exchange (SAX) and porous graphitic carbon (PGC) fractionation strategies. We applied this workflow to analyze the whole-cell phosphoproteome of the fission yeast Schizosaccharomyces pombe. Using the strategy, we identified 8353 phosphosites from which 1274 were newly identified. This provides the sig-nificant addition to the S. pombe phosphoproteome. Results of our study highlight that combining of PGC and SAX fractionation strategies substantially increases the robustness and specificity of LFQ phosphoproteomics. Overall, the presented LFQ phosphoproteomics workflow opens the door for studies that would get better insight into the complexity of the protein kinase functions of the fission yeast S. pombe.

2021-02-12 | PXD023818 | Pride

Phosphoproteome profiling reveals molecular mechanisms of growth factor mediated kinase inhibitor resistance in cancer cells

Project description:Although substantial progress has been made regarding the use of molecularly targeted cancer therapies, resistance almost invariably develops and presents a major clinical challenge. To evade the selective pressure of kinase inhibitors, cells often activate bypass signaling tracks and become intrinsically resistant. Apart from intrinsic cellular adaptation, the tumor microenvironment can rescue cancer cells by growth factor mediated induction of pro-survival signaling. We show that EGFR inhibition by Gefitinib is counteracted by several growth factors notably FGF2 and we assessed the global consequences of FGF2-mediated Gefitinib resistance at the proteome and phosphoproteome level. Multiplexed tandem mass tag (TMT) peptide labeling in conjunction with high resolution tandem mass spectrometry allowed the identification and quantification of ~22,000 phosphopeptides and ~8,800 proteins in biological triplicates without missing values. The data shows that Gefitinib treated cells are forced into developing intrinsic resistance by reprogramming of the proteome and phosphoproteome, whereas co-treatment with FGF2 largely reverted these changes to resemble the molecular composition of untreated cells. Simultaneous small molecule EGFR and FGFR inhibition overcomes FGF2 induced Gefitinib resistance and the phosphoproteomic experiments further prioritized the RAS/MEK/ERK axis as well as the PI3K/mTOR axis for combination treatment. Consequently, the MEK inhibitor Trametinib prevented FGF2-mediated survival of EGFR inhibitor resistant cells when used in combination with Gefitinib. Surprisingly, the pase II PI3K/mTOR inhibitor GSK2126458 reversed resistance mediated by all four growth factors tested, making it an interesting candidate for targeting the survival signals provided by the tumor microenvironment.

2022-03-01 | PXD004007 | Pride

ATLANTIC: Activity landscapes of tumor cell lines determine drug responses

Project description:Analysis of cancer cell line (CCL) genomes, proteomes and phenotypic drug responses are emerging approaches to uncover molecular mechanisms of drug action. We extended this paradigm to measuring proteome activity landscapes by integrating quantitative data for 10,000 proteins and 55,000 phosphorylation sites from 125 CCLs with large drug sensitivity data collections. To engage the scientific community in mining the thousands of novel functional associations generated by this work, we provide an interactive web resource termed ATLANTIC (http://atlantic.proteomics.wzw.tum.de). For instance, we found that Progesterone Receptor (PGR) phosphorylation is a stronger drug response predictor than PGR expression alone in hormone receptor positive breast cancer patients. We also demonstrate that Adenylate kinase isoenzyme 1 (AK1) inactivates chemotherapeutic drugs such as Cytarabine. Consequently, high AK1 levels correlated with poor survival of Cytarabine-treated acute myelogenous leukemia patients qualifying AK1 as a treatment stratification and drug response marker and possibly as a drug target.

2020-07-27 | PXD013615 | Pride

Adaptive resistance to Afatinib in non-small cell lung cancer cells in attenuated by Ca2+ depletion

Project description:Targeted therapies against oncogenic receptor tyrosine kinases are showing promising results in the clinic. However, despite the initial response, most patients become resistant. The majority of research regarding resistance has been focused on acquired resistance occurring after an extensive time of treatment. This has resulted in the development of combination treatments. Yet, the question remains how cells are able to survive initial treatment. We hypothesize that early resistance to apoptosis will enable cells to develop any growth stimulating mechanism. Our results show that regardless of an initial drug response, drug sensitive cells rapidly adapted to targeted therapy. Within days they continued to proliferate, despite persisting target inhibition. The Non-small Cell Lung Cancer (NSCLC) PC9 cell line was used for analysis of its full proteome, kinome and phospho-proteome during early adaptive resistance development against the EGFR targeted Tyrosine Kinase Inhibitor (TKI) Afatinib. The proteomics data showed an increase in abundance and activity of cytoskeleton and calcium signaling related proteins. In addition, cells showed a distinct morphological change. We found that if cells were deprived from calcium in order to restrict them from reorganizing their cytoskeleton, they were no longer able to survive TKI treatment. This could be validated on four different NSCLC cell lines, bearing different genetic backgrounds and sensitivities to initial TKI treatment targeting the EGFR. Therapeutically, increasing the efficiency of TKI treatment, and therefore early inhibition of adaption could potentially prevent further resistance development.

2018-10-02 | PXD008454 | Pride

Phosphoproteomic analysis of brain form Alzheimer’s disease

Project description:Alzheimer's disease (AD), the most common neurodegenerative disorder caused by neuronal loss which results in memory loss. Formation of neurofibrillary tangles composed of abnormal hyper phosphorylation of tau protein is one of the major pathological hallmarks for AD. Several neurodegenerative disorders including AD are associated with abnormal protein phosphorylation events.

2021-09-08 | PXD010807 | Pride

ERRalpha mediates metabolic adaptations that drive lapatinib resistance in breast cancer (gene expression profiles)

Project description:Ablation of ERRalpha significantly delays ERBB2-induced mammary tumorigenesis and ERRalpha regulates genes of the ERBB2 amplicon. To further investigate the relationship between ERRalpha activity and RTK signaling, we depleted ERRalpha in SKBr3 cells upon serum starvation, EGF treatment or heregulin treatment. Inhibition of ERBB2 signaling using the RTK inhibitor lapatinib impacts on ERRalpha stability. Since we have shown that the development of lapatinib-resistance restaures the expression of ERRalpha in breast cancer cells, we performed depletion of ERRalpha in SKBr3 cells that have developped resistance to lapatinib treatment in order to identify a potential reprogramming of ERRa transcriptional activity associated to lapatinib resistance,

2016-06-15 | GSE81546 | GEO

Homo sapiens

Project description:Acquired resistance to lapatinib

| PRJNA167755 | ENA

DUSP6 inhibition overcomes Neuregulin/HER3-driven therapy resistance in HER2+ breast cancer [BT474]

Project description:To investigate transcriptomic changes during development of resistance to lapatinib in a HER2+ breast cancer cell line We performed gene expression profiling analysis using data obtained from RNA-seq of 4 different stage of development of lapatinib resistance in a HER2+ breast cancer cell line

2024-04-13 | GSE231525 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data