Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The kinase PLK1 promotes the development of Kras/Tp53-mutant lung adenocarcinoma through transcriptional activation of the receptor RET

ABSTRACT: To investigate the function of PLK1 in the regulation of lung cancer development in mice, we performed genetic crosses to incorporate a Plk1 transgene into the KP mouse model (herein KPP) . We then performed gene expression profiling analysis using data from RNA-seq of tumors from either cohort respectively.

ORGANISM(S): Mus musculus

PROVIDER: GSE206644 | GEO | 2022/12/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The kinase PLK1 promotes the development of <i>Kras</i>/<i>Tp53</i>-mutant lung adenocarcinoma through transcriptional activation of the receptor RET.

Project description:Increased abundance of polo-like kinase 1 (PLK1) is observed in various tumor types, particularly in lung adenocarcinoma (LUAD). Here, we found that PLK1 accelerated the progression of LUAD through a mechanism that was independent of its role in mediating mitotic cell division. Analysis of human tumor databases revealed that increased PLK1 abundance in LUAD correlated with mutations in KRAS and p53, with tumor stage, and with reduced survival in patients. In a mouse model of KRASG12D-driven, p53-deficient LUAD, PLK1 overexpression increased tumor burden, decreased tumor cell differentiation, and reduced animal survival. PLK1 overexpression in cultured cells and mice indirectly increased the expression of the gene encoding the receptor tyrosine kinase RET by phosphorylating the transcription factor TTF-1. Signaling by RET and mutant KRAS in these tumors converged to activate the mitogen-activated protein kinase (MAPK) pathway. Pharmacological inhibition of the MAPK pathway kinase MEK combined with inhibition of either RET or PLK1 markedly suppressed tumor growth. Our findings show that PLK1 can amplify MAPK signaling and reveal a potential target for stemming progression in lung cancers with high PLK1 abundance.

| S-EPMC9737055 | biostudies-literature

Phosphoproteomic analysis of GEMM derived mouse lung adenocarcinoma cell lines - Kras G12D;tp53 KO vs Kras G12D;tp53 KO;Lkb1 KO

Project description:phospho-proteomic analysis of GEMM-derived mouse Lung adenocarcinoma cell-lines: KP vs KPL.

2023-01-24 | MSV000091133 | MassIVE

Total proteomic analysis of GEMM derived mouse lung adenocarcinoma cell lines - Kras G12D;tp53 KO vs Kras G12D; tp53 KO; Lkb1 KO

Project description:Total proteomic analysis of GEMM-derived mouse LUAD cell-lines: KP vs KPL

2023-01-24 | MSV000091131 | MassIVE

The kinase PLK1 promotes the development of Kras/Tp53-mutant lung adenocarcinoma through transcriptional activation of the receptor RET

Project description:The kinase PLK1 promotes the development of Kras/Tp53-mutant lung adenocarcinoma through transcriptional activation of the receptor RET

| PRJNA851712 | ENA

Expression profile in Plk1(+/-) aortas

Project description:Transcriptional profiling of mouse aortas comparing control wild-type animals with aortas from three different Plk1(+/-) mice. Goal was to determine the effects of Plk1 haploinsufficiency in aorta expression profiles.

2017-07-01 | GSE85199 | GEO

Ezetimibe derivative L14-8 suppresses advanced prostate cancer by activating PLK1/TP53-SAT1-induced ferroptosis

Project description:Androgen receptor signaling inhibitors (ARSIs) have demonstrated a survival benefit in metastatic prostate cancer (PCa). However, patients taking these agents inevitably acquire resistance and even develop neuroendocrine prostate cancer (NEPC), in which stage, the AR signaling is inactive, and therapies are limited for these lethal cases. Therefore, there is an urgent need to develop novel treatments to improve patient outcomes. Here we report that L14-8, a small molecule derived and optimized from ezetimibe, significantly suppressed prostate cancer growth by inducing ferroptosis in vitro and in vivo without obvious toxicity. Further mechanism studies demonstrate that L14-8 bound to and enhanced the stability of PLK1 and promoted the phosphorylation and expression of TP53, which enhanced its enrichment at the promoter of SAT1, a ferroptosis inducer, and increased its transcriptional activity. Overall, our studies developed a novel anti-tumor agent for treating lethal prostate cancer in an AR-independent manner and provided mechanistic insights into its action by targeting the PLK1-mediated TP53-SAT1 axis-induced ferroptosis.

2024-09-17 | GSE276906 | GEO

PLK1 signaling coopereates with estrogen receptor-dependent gene transcription.

Project description:Analysis of MCF7 breast cancer cells treated with estadiol for 6 h in presence or absence of the specific PLK1 inhibitor BI2536. Together with CHIP and global phosphoproteome data, the results demonstrate a key role of PLK1 in the estrogen receptor-mediated gene response. Hormone-deprived MCF7 cells were pretreated with BI2536 or vehicle (DMSO) followed by induction with estradiol (E2) or vehicle (ethanol). RNA of each condition was analysed in triplicate on an Agilent Human genome 4x44k v2 microarray [note: MCF7_DMSO_E2_rep3 sample was a clear technical outlier (poor hybridization), and was therefore excluded from the further analysis/this record].

2014-01-01 | E-GEOD-46856 | biostudies-arrayexpress

Genetic enhancers of partial PLK1 inhibition reveal hypersensitivity to kinetochore perturbations

Project description:Polo-like kinase 1 (PLK1) is a serine/threonine kinase required for mitosis and cytokinesis. As cancer cells are often hypersensitive to partial PLK1 inactivation, chemical inhibitors of PLK1 have been developed and tested in clinical trials. However, these molecules alone were not completely effective. PLK1 promotes numerous molecular and cellular events in the cell division cycle. To date, it is unclear which of these events most crucially depend on PLK1 activity. We used a CRISPR-based genome-wide screening strategy to identify genes whose inactivation enhances cell proliferation defects upon partial chemical inhibition of PLK1. Genes identified encode proteins that are functionally linked to PLK1 in multiple ways. Among them, factors that promote centromere and kinetochore function were clearly enriched. In particular, inactivation of the kinesin KIF18A or SKA1 in PLK1-compromised cells results in mitotic defects, activation of the spindle assembly checkpoint and nuclear reassembly defects. Our results suggest that functions of PLK1 at kinetochores are most sensitive to its inhibition, and point at KIF18A as a possible target for combinatorial therapies using existing PLK1 inhibitors.

2023-10-02 | GSE228155 | GEO

Epigenome analysis of normal and PLK1 knockdown samples

Project description:The Illumina Infinium 850k Human DNA methylation Beadchip was used to obtain DNA methylation profiles in normal and PLK1 knockdown DU145 cell samples. Samples included normal and PLK1 knockdown DU145 cell samples, Each sample is repeated three times.

2022-02-22 | GSE167261 | GEO

Role of PLK1 in epithelial-mesenchymal transition in human melanoma

Project description:Polo-like kinase 1 (PLK1), a serine/threonine kinase and important cell cycle regulator, is overexpressed in melanoma and its expression has been associated with poor disease prognosis. PLK1 has been shown to interact with NUMB, a NOTCH antagonist. However, the exact role of PLK1-NUMB-NOTCH axis in epithelial-mesenchymal transition (EMT) and melanoma progression is unclear. In this study, Affymetrix microarray analysis was performed to determine differentially expressed genes following doxycyclin induced shRNA-mediated knockdown of PLK1 in human melanoma cells that showed significant modulations in EMT and metastasis related genes.

2024-01-01 | GSE237385 | 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