Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

LC-MS/MS analysis of ALOX15B-binding protein in KRAS-mutant PDAC tissues

ABSTRACT: In our study, we demonstrated that downregulation of arachidonate 15-lipoxygenase (ALOX15B) promotes KRASmut-PDAC tumour growth. In order to elucidate the mechanisms underlying downregulation of ALOX15B promoting KRASmut-PDAC progression, quantitative proteomics mass-spectrometry(MS) analysis of differential proteins in KRAS-mutant tissues was performed

ORGANISM(S): Homo Sapiens

SUBMITTER: Jun Li

PROVIDER: PXD058462 | iProX | Mon Dec 02 00:00:00 GMT 2024

REPOSITORIES: iProX

ACCESS DATA

Json Xml

Similar Datasets

LC-MS/MS analysis of differential proteins in KRAS-mutant tissues

Project description:86%–90% of pancreatic ductal adenocarcinoma (PDAC) harbor activating mutations in KRAS, which regulate multiple carcinogenic signaling pathways. In order to elucidate the mechanisms underlying KRAS mutation-driven development and progression of PDAC, quantitative proteomics mass-spectrometry(MS) analysis of differential proteins in KRAS-mutant tissues was performed.

2024-11-29 | PXD058402 |

Determining the KRAS-regulated kinome in PDAC

Project description:Oncogenic KRAS drives cancer growth by activating diverse signaling networks, not all of which have been fully delineated. We set out to establish a system-wide profile of the KRAS-regulated kinase signaling network (kinome) in KRAS-mutant pancreatic ductal adenocarcinoma (PDAC). We knocked down KRAS expression in a panel of six cell lines, and then applied Multiplexed Inhibitor Bead/Mass Spectrometry (MIB/MS) chemical proteomics to monitor changes in kinase activity and/or expression. We hypothesized that depletion of KRAS would result in downregulation of kinases required for KRAS-mediated transforming activities, and in upregulation of other kinases that could potentially compensate for the deleterious consequences of the loss of KRAS. We identified 15 upregulated and 13 downregulated kinases in common across the panel. In agreement with our hypothesis, all 15 of the upregulated kinases have established roles as cancer drivers (e.g., SRC, TGFBR1, ILK), and pharmacologic inhibition of the upregulated kinase, DDR1, suppressed PDAC growth. Interestingly, 11 of the 13 downregulated kinases have established driver roles in cell cycle progression, particularly in mitosis (e.g., WEE1, Aurora A, PLK1). Consistent with a crucial role for the downregulated kinases in promoting KRAS-driven proliferation, we found that pharmacologic inhibition of WEE1 also suppressed PDAC growth. The unexpected paradoxical activation of ERK upon WEE1 inhibition led us to inhibit both WEE1 and ERK concurrently, which caused further potent growth suppression and enhanced apoptotic death than WEE1 inhibition alone. We conclude that system-wide delineation of the KRAS-regulated kinome can identify potential therapeutic targets for KRAS-mutant pancreatic cancer.

2022-02-17 | PXD025819 | Pride

TLR2 promotes tumour proliferation in KRAS-dependant PDAC in the absence of ARF6

Project description:TLR2 promotes tumour proliferation in KRAS-dependant PDAC in the absence of ARF6

| PRJNA1039267 | ENA

TLR2 promotes tumour proliferation in KRAS-dependant PDAC in the absence of ARF6

Project description:Metastasis is responsible for nearly 90% of all cancer-related deaths. Despite global efforts to prevent aggressive tumours, cancers such as pancreatic ductal adenocarcinoma (PDAC) are poorly diagnosed in the primary stage, resulting in lethal metastatic disease. RAS mutations are known to promote tumour spread, with mutant KRAS present in almost 90% of cases. Until recently, mutant KRAS remained untargeted and, despite the recent development of inhibitors, results show that tumour cells develop resistance. Another strategy for targeting mutant KRAS-dependent PDAC metastasis may come from targeting the downstream effectors of KRAS. One such axis, which controls tumour proliferation, invasiveness and immune evasion, is represented by ARF6-ASAP1. Here we show that targeting ARF6 results in adaptive rewiring that can restore proliferation and invasion potential over time. Using time-series RNA and ATAC sequencing approaches, we identified TLR-dependent NFκB, TNFα and hypoxia signalling as key drivers of adaptation in ARF6-depleted KRAS-dependent PDAC. Using in vitro and in vivo assays, we show that knocking down TLR2 with ARF6 significantly reduces proliferation, migration and invasion. Taken together, our data shed light on a novel co-targeting strategy with the therapeutic potential to counteract PDAC proliferation and metastasis.

2023-12-02 | GSE247513 | GEO

Endosomal trafficking bypassed by RAB5B-CD109 interplay promotes axonogenesis in KRAS-mutant pancreatic cancer

Project description:Perineural invasion (PNI) represents a unique biological feature causing the poor prognosis of pancreatic ductal adenocarcinoma (PDAC), especially with KRAS mutation. Extracellular vesicle (EVs)-packaged circRNAs function as essential mediator for tumor microenviroment communication to trigger PDAC cells invading into the surrounding regions and lead to distant metastasis. However, the regulatory mechanism of exosomal circRNA in PNI of KRAS-mutated PDAC has not been elucidated. Herein, we identified an KRASG12D-mutation responsive exosomal circRNA-circPNIT, which was positively correlated with PNI of PDAC. Functionally, KRASG12D PDAC-derived EV-packaged circPNIT promotes axonogenesis and PNI both in vitro and in vivo. Mechanistically, circPNIT-mediated Rab5B-CD109 interplay bypassed traditional endosomal trafficking to anchor Rab5B in the lipid rafts of multivescular body and fostered the secretion of circPNIT as a cargo of CD109+EVs. Subsequently, CD109+EVs achieved the targeted delivery of circPNIT to neurons by recognizing their surface receptor TRPV1 and facilitated DSCAML1 transcription-induced axonogenesis, which in turn enhanced the PNI by activating GFRα1/RET pathway. Importantly, we established an engineered si-cirPNIT-loaded CD109+EVs to dramatically inhibit PNI of PDAC in a KRASG12D/+ Trp53R172H/+ Pdx-1-Cre mice model. Collectively, Our findings highlight the mechanism underlying EV-packaed circRNA mediating PNI of KRAS mutated-PDAC dependent of a Rab5B endosomal bypass, supporting circPINT as an effective target for the treatment of neuro-metastatic PDAC

2024-12-27 | GSE251916 | GEO

Analysis of Nucleolin depletion impact on the KRAS-induced proteomic changes in mouse Pancreatic ductal adenocarcinoma cells.

Project description:To reveal the role of Nuclelin (Ncl) downstream of mutant KRAS in shaping the proteome of Pancreatic Ductal Adenocarcinoma (PDAC) cells, we carried out a quantitative proteomics analysis of tumour cells isolated from an inducible mouse model of PDAC (iKras PDAC) (Ying et al., 2012). In this model, oncogenic Kras (G12D) expression can be controlled by administration of doxycycline (Dox). Tandem Mass Tagging (TMT) was employed for quantitative analysis of Dox induced (24hrs) vs. non-induced iKras-PDAC cells, from control or Nucleolin depleted settings. Two independent siRNA oligos were used against Ncl. All samples barcoded and pooled together using TMT 6plex labelling kit (Thermo).

2023-02-12 | PXD038338 | Pride

TGFbeta treatment drives iKPC PDAC cells to bypass KRAS* dependency

Project description:TGFbeta promotes the bypass of KRAS* dependency in PDAC. To dissect the molecular mechanisms that regulated by TGFbeta in PDAC cells, we conducted RNA-seq analysis of iKPC PDAC cells with or without TGFbeta treatment.

2020-04-27 | GSE149130 | GEO

Gene expression differences between the pancreatic tissues of Pdx1-Cre;KrasLSL-G12D and Pdx1-Cre;KrasLSL-G12D;IKK2/betaF/F mice

Project description:Constitutive Kras and NF-kappaB activation is identified as signature alterations in human pancreatic ductal adenocarcinoma (PDAC). However, the mechanisms of constitutive NF-kappaB activation in KrasG12D-induced PDAC are not yet understood. Here, we report that pancreas-targeted IKK2/beta inactivation inhibited NF-kappaB activation and completely suppressed PDAC development in KrasG12D and KrasG12D;Ink4a/Arf mutant mice, demonstrating a genetic link between IKK2/beta and KrasG12D in PDAC inception. Our findings reveal that KrasG12D-activated AP-1 induces IL-1alpha, which in turn activates NF-kappaB and its target genes IL-1alpha and p62, to initiate IL-1alpha/p62 feedforward loops for inducing and sustaining NF-kappaB activity. Furthermore, IL-1alpha overexpression correlates with Kras mutation, constitutive NF-kappaB activity, and poor survival in PDAC patients. Therefore, our findings establish a pathway linking duel feedforward loops of IL-1alpha/p62 through which IKK2/beta/NF-kappaB is activated by KrasG12D. To study Kras-induced inflammatory responses and to identify differentially expressed genes between the pancreatic tissues of Pdx1-Cre;KrasLSL-G12D and Pdx1-Cre;KrasLSL-G12D;IKK2/betaF/F mice, cDNA microarray analysis was performed.

2012-01-24 | E-GEOD-27478 | biostudies-arrayexpress

Quantitative timecourse proteomics analysis of oncogenic KRAS removal in mouse Pancreatic Ductal Adenocarcinoma Cells

Project description:To reveal the impact of mutant KRAS on the proteome of Pancreatic Ductal Adenocarcinoma (PDAC) cells, we carried out a quantitative phospho-proteomic analysis of tumour cells isolated from an inducible mouse model of PDAC (iKras PDAC) (Ying et al., 2012). In this model, oncogenic Kras (G12D) expression can be controlled by administration of doxycycline (Dox). A timecourse Dox removal experiment was carried out in which cells with or without Dox removal at 12, 24, 36, and 48 hrs intervals were lysed and analysed by quantitative proteomics using Tandem Mass Tagging (TMT). Two independent biological replicate experiments were carried out, with timecourse samples in each replicate being barcoded and pooled together using TMT 10plex labelling kit (Thermo).

2023-02-12 | PXD038441 | Pride

RNAseq data comparing GFP, wildtype USP21 and enzyme-dead USP21 overexpressing iKPC PDAC cells with KRAS* expression (on dox) and KRAS* extinction (off dox)

Project description:USP21 promotes PDAC tumor cells to bypass KRAS* dependency. To dissect the molecular mechanism, we conducted RNA-seq analysis comparing iKPC cancer cells overexpressing GFP, wildtype USP21 and enzyme-dead USP21 at day 3 after KRAS* extinction. KRAS*-expressing iKPC cells with GFP overexpression are positive control.

2021-09-17 | GSE178860 | 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