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

PROVIDER: PRJNA851712 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR19779824_1.fastq.gz	Fastqsanger.gz
	SRR19779824_2.fastq.gz	Fastqsanger.gz
	SRR19779825_1.fastq.gz	Fastqsanger.gz
	SRR19779825_2.fastq.gz	Fastqsanger.gz
	SRR19779826_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 24

Similar Datasets

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

Project description: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.

2022-12-14 | GSE206644 | GEO

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

Transcriptomic profiling of oncogenic KRAS and TP53 in lung adenocarcinoma cells

Project description:Based on the previous eVIP study (Cancer Cell, 2016), we profiled the transcriptomes of lung adenocarcinoma cell lines expressing oncogenic KRAS and TP53 to compare methods and investigate the effects of these oncogenes on the cells' whole transcriptomes.

2021-10-01 | GSE183670 | 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

Transcriptomic profiling of oncogenic KRAS and TP53 in lung adenocarcinoma cells

Project description:Transcriptomic profiling of oncogenic KRAS and TP53 in lung adenocarcinoma cells

| PRJNA761664 | ENA

KRAS mutation-associated gene expression, p53 and STK11 mutations, proliferation and immune surveillance in lung adenocarcinoma

Project description:While mutations in the KRAS oncogene are amongst the most prevalent in human cancer, there are few successful treatments to target these tumors. It is also likely that heterogeneity in KRAS-mutant tumor biology significantly contributes to the response to therapy. We hypothesized that presence of commonly co-occurring mutations in STK11 and TP53 tumor suppressors may represent a significant source of heterogeneity in KRAS-mutant tumors. To address this, we utilized a large cohort of resected tumors from 442 lung adenocarcinoma patients with data including annotation of prevalent driver mutations (KRAS, EGFR) and tumor suppressor mutations (STK11 and TP53), microarray-based gene expression and clinical covariates including overall survival (OS). Specifically, we determined impact of STK11 and TP53 mutations on a new KRAS mutation-associated gene expression signature as well as previously defined signatures of tumor cell proliferation and immune surveillance responses. Interestingly, STK11, but not TP53 mutations, were associated with highly elevated expression of KRAS mutation-associated genes. Mutations in TP53 and STK11 also impacted tumor biology regardless of KRAS status, with TP53 strongly associated with enhanced proliferation and STK11 with suppression of immune surveillance. These findings illustrate the remarkably distinct ways through which tumor suppressor mutations may contribute to heterogeneity in KRAS-mutant tumor biology. In addition, these studies point to novel associations between gene mutations and immune surveillance that could impact the response to immunotherapy.

2015-10-21 | GSE72094 | GEO

RET Kinase Inhibition in Neuroendocrine Prostate Cancer, part 2

Project description:Increased treatment of metastatic castration resistant prostate cancer (mCRPC) with second-generation anti-androgen therapies (ADT) has coincided with a greater incidence of lethal, aggressive variant prostate cancer (AVPC) tumors that have lost androgen receptor (AR) signaling. AVPC tumors may also express neuroendocrine markers, termed neuroendocrine prostate cancer (NEPC). Recent evidence suggests kinase signaling may be an important driver of NEPC. To identify targetable kinases in NEPC, we performed global phosphoproteomics comparing AR-negative to AR-positive prostate cancer cell lines and identified multiple altered signaling pathways, including enrichment of RET kinase activity in the AR-negative cell lines. Clinical NEPC and NEPC patient derived xenografts displayed upregulated RET transcript and RET pathway activity. Pharmacologically inhibiting RET kinase in NEPC models dramatically reduced tumor growth and cell viability in mouse and human NEPC models. Our results suggest that targeting RET in NEPC tumors with high RET expression may be a novel treatment option.

2020-05-29 | PXD012971 | Pride

RET Kinase Inhibition in Neuroendocrine Prostate Cancer, part 1

2020-05-29 | PXD012970 | Pride

RET fusion genes, BCR-RET and FGFR1OP-RET, are associated with chronic myelomonocytic leukemia, display sensitivity to Sorafenib, an inhibitor of tyrosine-kinase activity and enhance monocytic differentiation

Project description:Myeloproliferative neoplasms are frequently associated with aberrant constitutive tyrosine kinase (TK) activity resulting from point mutations or chimaeric fusion genes, such as BCR ABL1 or JAK2 V617F. We report here for the first time in hematological malignancies, two novel fusion genes involving the TK RET, BCR-RET and FGFR1OP-RET, in chronic myelo monocytic leukemia (CMML) cases. The two RET fusion genes lead to the aberrant activation of RET, are able to transform hematopoietic cells and skew the hematopoietic differentiation program towards the monocytic/macrophage lineage. We also report that the BCR-RET fusion protein is insensitive to Imatinib but sensitive to Sorafenib in vivo. CMML is an hematopoietic malignancy associated with the frequent activation of the RAS pathway. The RET fusion genes seems to constitutively mimic the same signaling pathway than RAS mutations. Overall, the RET fusion genes behaviors in the monocytic lineage underlie the role of the normal RET TK activity during the physiological monocytic differentiation. We analysed BAF/3 cells infected by BCR-RET, FGFR1OP-RET or BCR-ABL1P210 fusion genes retroviruses and sorted out using EGFP fluorescence, with Affymetrix GeneChip MouseGene 1.0 ST platform.

2012-01-06 | E-GEOD-34900 | biostudies-arrayexpress

2012-01-06 | GSE34900 | GEO