Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Identification of Src Family Kinases as potential therapeutic targets for chemotherapy-resistant triple negative breast cancer

ABSTRACT: Identification of Src Family Kinases as potential therapeutic targets for chemotherapy-resistant triple negative breast cancer

PROVIDER: PRJNA842404 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR19403600.fastq.gz	Fastqsanger.gz
	SRR19403601.fastq.gz	Fastqsanger.gz
	SRR19403602.fastq.gz	Fastqsanger.gz
	SRR19403603.fastq.gz	Fastqsanger.gz
	SRR19403604.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 64

Similar Datasets

Identification of Src Family Kinases as potential therapeutic targets for chemotherapy-resistant triple negative breast cancer

Project description:Neoadjuvant chemotherapy (NAC) remains the cornerstone of treatment for triple negative breast cancer (TNBC) with the goal of complete eradication of disease. However, for patients with residual disease after NAC, recurrence and mortality rates are high and identification of novel therapeutic targets are urgently needed. Here we quantified tyrosine phosphorylation (pTyr) mediated signaling networks in chemotherapy sensitive (CS) and resistant (CR) TNBC patient derived xenografts (PDX) to gain novel therapeutic insights. We identified Src Family Kinases (SFKs) as potential therapeutic targets in CR TNBC PDXs. Treatment with dasatinib, an FDA approved SFK inhibitor, led to inhibition of tumor growth in vivo. Further analysis of post-treatment PDXs revealed multiple mechanisms of actions of the drug confirming the multi-target inhibition of dasatinib. Direct analysis of pTyr in tumor specimens from TNBC patients suggest a low prevalence of SFK driven tumors in the clinic which may explain why clinical trials evaluating dasatinib failed in unselected breast cancer patients. Taken together, these results underscore the importance of pTyr characterization of tumors in identifying new targets as well as stratifying patients based on their activated signaling networks for therapeutic options. Our data also suggest that treatment with an SFK inhibitor may benefit a subset of TNBC patients with CR disease.

2022-09-20 | GSE204825 | GEO

Src Family Kinases as potential therapeutic targets for chemotherapy-resistant triple negative breast cancer

Project description:Here we quantified tyrosine phosphorylation (pTyr) mediated signaling networks in chemotherapy sensitive (CS) and resistant (CR) TNBC patient derived xenografts (PDX) to gain novel therapeutic insights. We identified Src Family Kinases (SFKs) as potential therapeutic targets in CR TNBC PDXs. Additionally, we performed pTyr analysis on tumor specimens derived from TNBC patients and observed lower prevalence of SFK driven tumors.

2022-10-13 | PXD034154 | Pride

Transcription profiling of NIH3T3 cells treated with platelet-derived growth factor and Src kinase inhibitors to identify immediate early genes that are induced by PDGF through Src family kinases and other kinases.

Project description:This experiment was performed to identify immediate early genes that were induced by PDGF specifically through Src family kinases (SFKs), MEK1/2, or PI 3-K.

2007-09-22 | E-GEOD-2196 | biostudies-arrayexpress

Identification of Src Family Kinases as Potential Therapeutic Targets for Chemotherapy-Resistant Triple Negative Breast Cancer.

Project description:Neoadjuvant chemotherapy (NAC) remains the cornerstone of the treatment for triple negative breast cancer (TNBC), with the goal of complete eradication of disease. However, for patients with residual disease after NAC, recurrence and mortality rates are high and the identification of novel therapeutic targets is urgently needed. We quantified tyrosine phosphorylation (pTyr)-mediated signaling networks in chemotherapy sensitive (CS) and resistant (CR) TNBC patient-derived xenografts (PDX), to gain novel therapeutic insights. The antitumor activity of SFK inhibition was examined in vivo. Treated tumors were further subjected to phosphoproteomic and RNAseq analysis, to identify the mechanism of actions of the drug. We identified Src Family Kinases (SFKs) as potential therapeutic targets in CR TNBC PDXs. Treatment with dasatinib, an FDA approved SFK inhibitor, led to inhibition of tumor growth in vivo. Further analysis of post-treatment PDXs revealed multiple mechanisms of actions of the drug, confirming the multi-target inhibition of dasatinib. Analysis of pTyr in tumor specimens suggested a low prevalence of SFK-driven tumors, which may provide insight into prior clinical trial results demonstrating a lack of dasatinib antitumor activity in unselected breast cancer patients. Taken together, these results underscore the importance of pTyr characterization of tumors, in identifying new targets, as well as stratifying patients based on their activated signaling networks for therapeutic options. Our data provide a strong rationale for studying SFK inhibitors in biomarker-selected SFK-driven TNBC.

| S-EPMC9454481 | biostudies-literature

Characterization of the Src-regulated kinome identifies SGK1 as a key mediator of Src-induced transformation

Project description:Despite significant progress, our understanding of how specific oncogenes transform cells is still limited and likely underestimates the complexity of downstream signalling events. Herein, we describe a novel, integrated approach that addresses this knowledge gap. This utilizes mass spectrometry-based chemical proteomics to characterize the global impact of an oncogene on the expressed kinome, and then functionally annotates the regulated kinases. As an example, we identified approximately seventy protein kinases exhibiting altered expression and/or phosphorylation in Src-transformed mammary epithelial cells. An integrated siRNA screen identified nine kinases, including SGK1, as being essential for Src-induced transformation. In triple negative breast cancer cells, which exhibit a prominent signalling network governed by src family kinases, Src positively regulated SGK1 expression and combined inhibition of Src and SGK1 was more effective at inhibiting colony formation in vitro, and xenograft growth in vivo, than either treatment alone. Therefore, this approach not only provides major mechanistic insights into oncogenic transformation but also aids the design of improved therapeutic strategies.

2019-01-14 | PXD010687 | Pride

Response to Neoadjuvant Chemotherapy in Triple Negative Breast tumors.

Project description:In a cohort study of 7 women with primary invasive breast cancer, we obtained a tumor specimen before (biopsy) and after (tumorectomy) 4 cycles of NAC with epirubicine and cyclophosphamide, followed by 4 cycles of taxanes. Total RNA was extracted from tumor specimens and the whole transcriptome was quantified with Affymetrix HuGene1.1ST. Molecular functions changing during chemotherapy were searched. Whole genome expression of triple negative breast cancer tissues were measured before and after four cycles neoadjuvant chemotherapy

2016-03-24 | E-GEOD-43816 | biostudies-arrayexpress

XmaI-RRBS on triple negative breast carcinoma samples taken prior to chemotherapy

Project description:Triple negative breast carcinoma samples were taken prior to chemotherapy in order to identify epigenomic profiles predictive of neoadjuvant chemotherapy efficacy

2020-12-12 | GSE123712 | GEO

Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy

Project description:Triple negative breast cancer is a heterogeneous disease with distinct molecular subtypes that differentially respond to chemotherapy and targeted agents. The purpose of this study was to explore the clinical relevance of Lehmann triple negative breast cancer subtypes by identifying any differences in response to neoadjuvant chemotherapy among them.

2017-11-17 | GSE106977 | GEO

Tissue- and Pathway-Specific Metabolomic Profiles of the Steroid Receptor Coactivator (SRC) family

Project description:The rapidly growing family of coregulators of nuclear receptors includes coactivators that promote transcription and corepressors that harbor the opposing function. In recent years, coregulators have begun to emerge as important regulators of metabolic homeostasis, including the p160 Steroid Receptor Coactivator (SRC) family. Members of the SRC family have been ascribed important roles in control of gluconeogenesis in liver and fatty acid oxidation in skeletal muscle. To provide a deeper and more granular understanding of the metabolic impact of SRC family members, we have performed targeted metabolomics analysis of key metabolic byproducts of glucose, fatty acid, and amino acid metabolism in mice with global knockout of SRC-1, SRC-2, or SRC-3. We measured amino acids, acyl carnitines, and organic acids in five tissues with key metabolic functions (liver, heart, skeletal muscle, brain, plasma) isolated from SRC-1, -2, or -3 knockout mice and their wild-type littermates in the fed and fasted conditions, thereby unveiling unique metabolic functions of each SRC coactivator. Overall, we observed entire groups or subgroups of metabolites belonging to discrete metabolic pathways that were influenced in different tissues and/or feeding states due to ablation of individual SRC isoforms. Surprisingly, we identified very few metabolites that changed universally across the three SRC knockout models. These findings demonstrate that coactivator function has very limited redundancy even within the homologous SRC coactivator family. Furthermore, this work also demonstrates the use of metabolomics as a means for identifying novel metabolic regulatory functions of transcriptional coregulators.

2013-04-10 | MTBLS30 | MetaboLights

Identification and functional annotation of the Src-regulated kinome, part 2

Project description:Despite significant progress, our understanding of how specific oncogenes transform cells is still limited and likely underestimates the complexity of downstream signalling events. Herein, we describe a novel, integrated approach that addresses this knowledge gap. This utilizes mass spectrometry-based chemical proteomics to characterize the global impact of an oncogene on the expressed kinome, and then functionally annotates the regulated kinases. As an example, we identified approximately one hundred protein kinases exhibiting altered expression and/or phosphorylation in Src-transformed mammary epithelial cells. Screening with corresponding siRNAs identified nine kinases, including SGK1, as being essential for Src-induced transformation. In contrast, MAP4K5 suppressed transformation in a manner enhanced by S335 phosphorylation. In triple negative breast cancer cells, Src positively regulated SGK1 expression and combined inhibition of Src and SGK1 was more effective at inhibiting cell proliferation than either treatment alone. Therefore, this approach not only provides major mechanistic insights into oncogenic transformation but also aids the design of improved therapeutic strategies.

2018-11-21 | PXD011146 | Pride

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