See
Genome Information for Homo sapiens
Spheroids are 3D multi-cell aggregates formed in non-addherent culture conditions. In ovarian cancer (OC), they serve as a vehicle for cancer cell dissemination in the peritoneal cavity. We investigated genes and networks upregulated in three dimensional (3D) versus two-dimensional (2D) culture conditions by Affymetrix gene expression profiling and identified ALDH1A1, a cancer stem cell marker as being upregulated in OC spheroids. Network analysis confirmed ALDH1A1 upregulation in spheroids in direct connection with elements of the β-catenin pathway. A parallel increase in the expression levels of β-catenin and ALDH1A1 was demonstrated in spheroids vs. monolayers an in successive spheroid generations by using OC cell liness and primary OC cells. The percentage of Aldefluor positive cells was significantly higher in spheroids vs. monolayers in IGROV1, A2780, SKOV3, and primary OC cells. B-catenin knock-down decreased ALDH1A1 expression and chromatin immunoprecipitation demonstrated that β-catenin directly binds to the ALDH1A1 promoter. Both siRNA mediated β-catenin knock-down and a novel ALDH1A1 small molecule enzymatic inhibitor described here for the first time, decreased the number of OC spheroids (p<0.001) and cell viability. These data strongly support the role of β-catenin regulated ALDH1A1 in the maintenance of OC spheroids and of a stem cell phenotype and propose new ALDH1A1 inhibitors targeting this cell population.
Overall design: Different gene profiles were observed in ovarian cancer spheroids versus ovarian cancer monolayers. Nine samples were analyzed in triplicate. Each group is a reference.
Accession | PRJNA232817; GEO: GSE53759 |
Data Type | Transcriptome or Gene expression |
Scope | Multiisolate |
Organism | Homo sapiens[Taxonomy ID: 9606] Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo; Homo sapiens |
Publications | Condello S et al., "β-Catenin-regulated ALDH1A1 is a target in ovarian cancer spheroids.", Oncogene, 2015 Apr 30;34(18):2297-308 |
Submission | Registration date: 2-Jan-2014 iu school of medicine |
Relevance | Medical |
Project Data:
Resource Name | Number of Links |
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Publications |
PubMed | 1 |
PMC | 1 |
Other datasets |
GEO DataSets | 1 |
GEO Data DetailsParameter | Value |
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Data volume, Spots | 259821 |
Data volume, Processed Mbytes | 4 |
Data volume, Supplementary Mbytes | 36 |