Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene expression profiling of generated sunitinib-resistant RCC cell lines

ABSTRACT: The clinical response to sunitinib in advanced renal-cell carcinoma (RCC) is frequently limited in magnitude and duration due to drug resistance, but the underlying mechanisms remain elusive. To discover mechanisms of resistance, we developed drug-resistant cell lines and have their gene expressions profiled and compared. Results provide insight into the molecular mechanisms underlying sunitinib-resistance.

ORGANISM(S): Homo sapiens

PROVIDER: GSE69535 | GEO | 2016/09/30

SECONDARY ACCESSION(S): PRJNA285805

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Label-free quantitative phosphoproteomics of sunitinib-resistant renal cell carcinoma upon estrogen treatment

Project description:Sunitinib is a TKI inhibitor used for managing metastatic renal cell carcinoma (RCC). However, chronic sunitinib treatment in RCC usually results in the development of drug resistance via alternating phosphorylation dynamics. On the other hand, 17-beta-estradiol, or estrogen, has been demonstrated to repress RCC growth partly through regulating cell signallings. To investigate how estrogen can repress sunibitinib-resistant RCC growth and its the possible mechanism of action related protein phosphorylation, a label-free quantitative phosphoproteomics study is performed.

2020-08-07 | PXD011020 | Pride

Effect of depletion of FUS on gene expression during in sunitinib-resistance cell lines

Project description:To investigate the function FUS in the regulation of sunitinib-resistance， we used lentiviral transduction to knock down FUS expression in the sunitinib-resistant RCC cells.

2023-03-31 | GSE226245 | GEO

Transgelin contributes to a poor response of metastatic renal cell carcinoma to sunitinib treatment

Project description:Renal cell carcinoma (RCC) represents about 2-3% of all cancers with over 400,000 new cases per year. Sunitinib, a vascular endothelial growth factor tyrosine kinase receptor inhibitor, has been used mainly for first-line treatment of metastatic clear-cell RCC with good or intermediate prognosis. However, about one third of metastatic RCC patients do not respond to sunitinib, leading to disease progression. Here we aim to find and characterize proteins associated with poor sunitinib response in a pilot proteomics study. 16 RCC tumors from patients responding (8) vs. non-responding (8) to sunitinib in 3 months after treatment initiation, together with their adjacent non-cancerous tissues, were analyzed using data independent acquisition mass spectrometry. Proteomics analysis quantified 1996 protein groups (q<0.01) and revealed 27 proteins deregulated between tumors non-responding vs. responding to sunitinib, representing a pattern of deregulated proteins potentially contributing to sunitinib resistance. Gene set enrichment analysis showed up-regulation of epithelial-to-mesenchymal transition with transgelin as one of the most significantly abundant protein. Transgelin expression was silenced by CRISPR/Cas9 and RNA interference, and the cells with reduced transgelin level exhibited significantly slower proliferation. Our data indicate that transgelin is an essential protein supporting RCC cell proliferation which could contribute to intrinsic sunitinib resistance.

2021-11-03 | PXD027065 | Pride

Differentially expressed genes analysis between dihydroberberine, sunitinib and dihydroberberine plus sunitinib.

2015-06-26 | GSE70282 | GEO

Candidate biomarkers for treatment benefit from sunitinib in patients with advanced renal cell carcinoma using mass spectrometry-based (phospho)proteomics

Project description:The tyrosine kinase inhibitor sunitinib is an effective first-line treatment for patients with advanced renal cell carcinoma (RCC). Hypothesizing that a functional read-out by mass spectrometry-based (phospho, p-)proteomics will identify predictive biomarkers for treatment outcome of sunitinib, tumor tissues of 26 RCC patients were analyzed. Eight patients were primary resistant (RES) and 18 sensitive (SENS).

2024-01-26 | PXD043514 | Pride

Differentially expressed genes analysis between dihydroberberine, sunitinib and dihydroberberine plus sunitinib.

Project description:To gain insights into the mechanisms of dihydroberberine, sunitinib and dihydroberberine plus sunitinib on inhibition to A549 cells, we have employed whole genome microarray expression profiling as a discovery platform to identify different genes between dihydroberberine, sunitinib and dihydroberberine plus sunitinib-treated sample and control. A549 cells were cultivated in the absence or presence of 25?mol/L dihydroberberine, 2?mol/L sunitinib, 25?mol/L dihydroberberine plus 2?mol/L sunitinib for 48 h, followed by the Agilent Whole Human Genome Oligo Microarray

2015-06-26 | E-GEOD-70282 | biostudies-arrayexpress

Impact of sunitinib resistance on clear cell renal cell carcinoma therapeutic sensitivity in vitro

Project description:Sunitinib resistance creates a major clinical challenge for the treatment of advanced clear cell renal cell carcinoma (ccRCC) and functional and metabolic changes linked to sunitinib resistance are not fully understood. We sought to characterize the molecular and metabolic changes induced by the development of sunitinib resistance in ccRCC by developing and characterizing the transcriptome of two human ccRCC cell lines resistant to sunitinib.

2024-04-17 | GSE216494 | GEO

Project description:Mechanisms of acquired resistance to sunitinib in an RCC patient

| PRJNA493178 | ENA

Enhanced YB1/EphA2 axis signaling promotes acquired resistance to sunitinib and metastatic potential of renal cell carcinoma

Project description:VHL mutations are the most common tumorigenic lesions in clear cell renal cell carcinoma (ccRCC) and result in continued activation of the HIF/VEGF pathway and uncontrolled cancer progression. Receptor tyrosine kinase (RTK) inhibitors such as sunitinib have been demonstrated to target tumorigenic signaling pathways, delay tumor progression and improve patient prognosis in metastatic renal cell carcinoma (mRCC). Although several mechanisms of sunitinib resistance have been reported, the solutions to overcome this resistance remain still unclear. In our study, we found that increased expression of YB1 (Y box binding protein 1, a multidrug resistance associated protein) and EphA2 (a member of erythropoietin-producing hepatocellular (Eph) receptors, belonging to the RTK family) mediated sunitinib resistance and mRCC exhibited a large phenotypic dependence on YB1 and EphA2. In addition, our findings confirm that YB1 promotes the invasion, metastasis and sunitinib resistance of ccRCC by regulating the EphA2 signaling pathway. Furthermore, pharmacological inhibition of EphA2 through the small molecule inhibitor ALW-II-41-27 reduced the proliferation of sunitinib-resistant tumor cells and suppressed tumor growth in vivo and restored the sensitivity of sunitinib-resistant tumor cells to sunitinib in vitro and in vivo. Mechanistically, YB1 increases the protein levels of EphA2 by maintaining the protein stabilization of EphA2 through inhibiting the proteasomal degradation pathway. Collectively, our findings provide the theoretical rationale that ccRCC metastasis and RTK-directed therapeutic resistance could be prospectively and purposefully targeted.

2020-05-28 | GSE151336 | GEO

Cardiac Metabolic Deregulation Induced by the Tyrosine Kinase Receptor Inhibitor Sunitinib is rescued by Endothelin Receptor Antagonism

Project description:The growing field of cardio-oncology addresses the side effects of cancer treatment on the cardiovascular system. Here, we explored the cardiotoxicity of the antiangiogenic therapy, sunitinib, in the mouse heart from a diagnostic and therapeutic perspective. We showed that sunitinib induces an anaerobic switch of cellular metabolism within the myocardium which is associated with the development of myocardial fibrosis and reduced left ventricular ejection fraction as demonstrated by echocardiography. The capacity of positron emission tomography with [18F]fluorodeoxyglucose to detect the changes in cardiac metabolism caused by sunitinib was dependent on fasting status and duration of treatment. Pan proteomic analysis in the myocardium showed that sunitinib induced (i) an early metabolic switch with enhanced glycolysis and reduced oxidative phosphorylation, and (ii) a metabolic failure to use glucose as energy substrate, similar to the insulin resistance found in type 2 diabetes. Co-administration of macitentan, the endothelin receptor antagonist, to sunitinib-treated animals prevented both metabolic defects, restored glucose uptake and cardiac function, and prevented myocardial fibrosis. These results support the endothelin system in mediating the cardiotoxic effects of sunitinib and endothelin receptor antagonism as a potential therapeutic approach to prevent cardiotoxicity. Furthermore, metabolic and functional imaging can monitor the cardiotoxic effects and the benefits of endothelin antagonism in a theranostic approach.

2017-07-14 | PXD006888 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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