Filters
Technology
Platform
SRP041831
Homo sapiens
5 Downloadable Samples
IlluminaHiSeq2000
Description
The aim of this study is to identify the SPIN1 target genes in liposarcoma cells Overall design: Liposarcoma is one of the most common histological subtypes of soft tissue sarcoma and causes high incidence of morbidity and mortality. Since therapeutic options for liposarcoma treatment are insufficient, there is an urgent need to identify novel therapeutic targets. Here, we show that knockdown of SPIN1, a reader of H3K4me3 and H3R8me2a chromatin marks, strongly reduces proliferation and survival of liposarcoma cells in vitro and in xenograft mouse models. Combining genome-wide chromatin binding and transcriptome analyses, we found that SPIN1 in cooperation with the transcription factor MAZ directly enhances expression of GDNF, an activator of the RET signaling pathway. Accordingly, knockdown of SPIN1 results in reduced levels of GDNF and activated RET explaining diminished liposarcoma cell proliferation and survival. In line with these observations, levels of SPIN1, GDNF, and activated RET are highly increased in human liposarcoma compared to lipoma or normal adipose tissue. Importantly, SPIN1-mediated transcriptional control depends on binding to H3K4me3 suggesting that targeting of this interaction with small molecule inhibitors is a novel strategy to treat liposarcoma.
Publication Title
The histone code reader SPIN1 controls RET signaling in liposarcoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2500
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 ß3-KRAS signaling axis, which is involved in stem cell like properties, is abrogated upon KDM1A knockdown. Indeed, Integrin ß3 and its non-canonical ligand galectin-3 were strongly downregulated and their downstream NF-?B activity was decreased upon KDM1A knockdown. Finally, correlation of KDM1A to the Integrin ß3 level was validated in TMAs. Overall design: Determining the role of KDM1A in A549 cells, mRNA profiles of control and knockdown samples of A549 cells, generated by deep sequencing, in triplicate, using Illumina HiSeq 2500.
Publication Title
LSD1 modulates the non-canonical integrin β3 signaling pathway in non-small cell lung carcinoma cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Transient transfection of activated Notch1 (Notch1-ICD) decreases cellular proliferation and reduces the expression of a subset of neuroendocrine genes.
Publication Title
Comprehensive genomic profiles of small cell lung cancer.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples