Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA342818 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:KRAS mutations occur in approximately 25% of non-small cell lung cancer (NSCLC). They account for the therapy resistance to EGFR inhibitors and are suggested to be difficult to target by specific drugs. Therefore, new therapies for KRAS mutant NSCLC are urgently needed. The histone H3K4 and H3K9 di/mono-demethylase KDM1A is a key epigenetic writer, aberrantly upregulated in many cancer types, including NSCLC. In order to understand the functional role of KDM1A in the progression of lung adenocarcinoma, KDM1A expression profiles were analysed in tissue microarrays (TMAs) including 182 lung adenocarcinoma. KDM1A expression correlated with high grade and metastasized tumor. To investigate the impact of KDM1A in lung adenocarcinoma development, we used the KRAS mutated A549 cell line to establish a shRNA-mediated stable KDM1A knockdown cell clone. Unexpectedly, KDM1A knockdown had only a slight effect on retardation of cell growth. However, cell invasion and self-renewal capability was significantly decreased by KDM1A inhibition. KDM1A knockdown in A549 cell resulted in a dramatic change in the transcriptome profile as determined by RNA-Seq. Interestingly, genes involved in the KRAS signature and lung epithelial marker genes were significantly affected upon KDM1A knockdown. Ingenuity pathway analysis also suggested that the alternative integrin β3-KRAS signaling axis, which is involved in stem cell like properties, is abrogated upon KDM1A knockdown. Indeed, Integrin β3 and its non-canonical ligand galectin-3 were strongly downregulated and their downstream NF-κB activity was decreased upon KDM1A knockdown. Finally, correlation of KDM1A to the Integrin β3 level was validated in TMAs.
2017-03-13 | GSE86874 | GEO
Project description:The highest frequencies of KRAS mutations occur in colorectal carcinoma (CRC) and pancreatic ductal adenocarcinoma (PDAC). Therapeutically targeting downstream pathways mediating oncogenic properties of KRAS mutant cancers is limited by an incomplete understanding of the contextual cues modulating the signaling output of activated KRAS. We performed mass spectrometry on mouse tissues expressing wild-type or mutant KRAS to determine how tissue context and genetic background modulate oncogenic signaling. Mutant KRAS dramatically altered the proteomes and phosphoproteomes of pre-neoplastic and neoplastic colons and pancreases in a largely context-specific manner. We developed an approach to humanize the mouse networks with data from human cancer and identified genes within the CRC and PDAC networks synthetically lethal with mutant KRAS. Our studies demonstrate the context-dependent plasticity of oncogenic signaling, identify non-canonical mediators of KRAS oncogenicity within the KRAS-regulated signaling network, and demonstrate how statistical integration of mouse and human datasets can reveal cross-species therapeutic insights.
2019-06-28 | PXD013922 | Pride
Project description:Pancreatic ductal adenocarcinoma (PDAC) is characterised by an abundant desmoplastic reaction which includes an excess production of extracellular matrix and interacts with integrin adhesion receptors. Integrin adhesion complexes formed by HPDE cells (H6c7), with and without expression of mutant KRas G12V, were isolated and analysed by LC-MSMS
2022-05-20 | PXD027827 | Pride
Project description:The aim of the study was to investigate gene expression tumour progression of KRas*/MYC driven lung tumours from adenocarcinoma in situ to invasive disease.
2018-06-01 | E-MTAB-6432 | biostudies-arrayexpress
Project description:Oncogenic KRAS mutations are absent in approximately 10% of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) and may represent a subgroup of mPDAC with therapeutic options beyond standard-of-care cytotoxic chemotherapy. While distinct gene fusions have been implicated in KRAS wildtype mPDAC, information regarding other types of mutations remain limited, and gene expression patterns associated with KRAS wildtype mPDAC have not been reported. Here, we leverage sequencing data from the PanGen trial to perform comprehensive characterization of the molecular landscape of KRAS wildtype mPDAC and reveal increased frequency of chr1q amplification encompassing transcription factors PROX1 and NR5A2. By leveraging data from colorectal adenocarcinoma and cholangiocarcinoma samples, we highlight novel similarities between cholangiocarcinoma and KRAS wildtype mPDAC involving both mutation and expression-based signatures and validate these findings using an independent dataset. These data further establish KRAS wildtype mPDAC as a unique molecular entity, with therapeutic opportunities extending beyond gene fusion events.
2022-10-15 | PXD036632 | Pride
Project description:The purpose of this research is to understand the role and expand the precision medicine of EZH2 inhibition in lung adenocarcinoma. Our data show that histone methyltransferase EZH2 acts in a context-dependent manner as an oncogene or tumor suppressor in KRAS+/Trp53-null murine lung adenocarcinoma. Moreover, EZH2 deprivation confers sensitivity to histone demethylase and BET inhibitors in 3D culture and in vivo models, representing precision medicine strategies for lung cancers with low canonical EZH2 activity. We found that the embryonic lung transcription factor FOXP2 is de-repressed when EZH2 is inactivated, and FOXP2 promotes stemness and migration, making it a promising therapeutic target. Finally, we identified that high EZH2 correlated with high FOXP2 and poorly differentiated lung cancers, a subgroup that may benefit from combined EZH2 and BET inhibition.
2022-11-16 | GSE154689 | GEO
Project description:The purpose of this research is to understand the role and expand the precision medicine of EZH2 inhibition in lung adenocarcinoma. Our data show that histone methyltransferase EZH2 acts in a context-dependent manner as an oncogene or tumor suppressor in KRAS+/Trp53-null murine lung adenocarcinoma. Moreover, EZH2 deprivation confers sensitivity to histone demethylase and BET inhibitors in 3D culture and in vivo models, representing precision medicine strategies for lung cancers with low canonical EZH2 activity. We found that the embryonic lung transcription factor FOXP2 is de-repressed when EZH2 is inactivated, and FOXP2 promotes stemness and migration, making it a promising therapeutic target. Finally, we identified that high EZH2 correlated with high FOXP2 and poorly differentiated lung cancers, a subgroup that may benefit from combined EZH2 and BET inhibition.
2022-11-16 | GSE182819 | GEO
Project description:In order to determine the role of the transcription factor Arntl2 in regulating metastatic ability and identify Arntl2-dependent transcriptonal targets in metastatic lung adenocarcinoma, we sequenced the mRNA from 3 mouse metastasis cell lines. Each of these cell lines (482N1shLuciferase, 482N1shArntl2#1, and 482N1shArntl2#2) were derived from the same parental cell line, 482N1. 482N1 was derived from a lymph node metastasis of a Kras LSL G12D, p53 flox/flox 129S1/SvlmJ mouse model of metastatic lung adenocarcinoma. A comparison of shLuciferase and shArntl2 cell lines reveals Arntl2-dependent changes in the metastatic transcriptome.
2016-02-08 | GSE72942 | GEO
Project description:In order to determine the role of Cd109 in regulating metastatic ability and identify Cd109-dependent transcriptonal targets in metastatic lung adenocarcinoma, we sequenced the mRNA from 3 mouse metastasis cell lines. Each of these cell lines (889PF-shGFP, 889PF-shCd109#1, and 889PF-shCd109#2) were derived from the same parental cell line 889PF. 889PF was derived from the pleural fluid of a Kras LSL G12D, p53 flox/flox 129S1/SvlmJ mouse model of metastatic lung adenocarcinoma. A comparison of shGFP and shCd109 cell lines reveals Cd109-dependent changes in the metastatic transcriptome.
2017-02-06 | GSE84448 | GEO
Project description:Recent data suggests that repression of the Type II TGF-B Receptor (Tgfr2) repression in human lung adenocarcinoma is important for progression from noninvasive to invasive adenocarcinoma. To test this hypothesis in a animal model of non-invasive lung cancer, we generated an inducible, lung specific Tgfbr2 knockout model in the oncogenic Kras mouse. LSL-KrasG12D positive mice were simultaneously backcrossed to C57/Bl6 mice and to the Tgfbr2 flox/flox mice. To induce tumors, 100 _l of saline containing 3x10e10 particles of an adenovirus containing the Cre recombinase (Ad.Cre) was administered to each LSL-KrasG12D mouse intra-nasally. Mice were sacrificed at 7 weeks after administration of Adeno-Cre. We used laser capture microdissection to acquire tumor cells from KrasTgfbr2-/- and KrasTgfbr2 wt mouse tumors.
2011-09-14 | E-GEOD-27717 | biostudies-arrayexpress