Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression in colon cancer stem cells (CSC) cultures identified by Wnt signaling levels

ABSTRACT: Primary colon CSC cultures were transduced with a Wnt responsive construct (TOP-GFP) and were single cell cloned. 10% highest and lowest TOP-GFP cell fractions were FACS sorted and arrayed. Primary colon CSC cultures with a responsive construct (TOP-GFP): high and low TOP-GFP cell fractions. 4 samples.

ORGANISM(S): Homo sapiens

SUBMITTER: Louis Vermeulen

PROVIDER: E-GEOD-17375 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Wnt activity defines colon cancer stem cells and is regulated by the microenvironment.

Vermeulen Louis L De Sousa E Melo Felipe F van der Heijden Maartje M Cameron Kate K de Jong Joan H JH Borovski Tijana T Tuynman Jurriaan B JB Todaro Matilde M Merz Christian C Rodermond Hans H Sprick Martin R MR Kemper Kristel K Richel Dick J DJ Stassi Giorgio G Medema Jan Paul JP

Nature cell biology 20100425 5

Despite the presence of mutations in APC or beta-catenin, which are believed to activate the Wnt signalling cascade constitutively, most colorectal cancers show cellular heterogeneity when beta-catenin localization is analysed, indicating a more complex regulation of Wnt signalling. We explored this heterogeneity with a Wnt reporter construct and observed that high Wnt activity functionally designates the colon cancer stem cell (CSC) population. In adenocarcinomas, high activity of the Wnt pathw ...[more]

PMID: 20418870

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Project description:Cancer stem cells (CSCs) have been reported in various cancers including skin squamous cell carcinoma (SCC). The molecular mechanisms regulating tumour initiation and stemness are still poorly characterized. Here, we found that Sox2, a transcription factor expressed in various types of embryonic and adult stem cells (SCs), was the most upregulated transcription factor in CSCs of squamous skin tumours. Sox2 is absent in normal epidermis and begins to be expressed in the vast majority of mouse and human pre-neoplastic skin tumours and continues to be expressed in a heterogeneous manner in invasive mouse and human SCCs. In contrast to other SCCs, in which Sox2 is frequently genetically amplified, the expression of Sox2 in mouse and human skin SCCs is transcriptionally regulated. Conditional deletion of Sox2 in the mouse epidermis dramatically decreases skin tumour formation following chemical induced carcinogenesis. Using Sox2-GFP knockin mice, we showed that Sox2 expressing cells in invasive SCC are greatly enriched in tumour propagating cells (TPCs) that further increase upon serial transplantations. Lineage ablation of Sox2 expressing cells within primary benign and malignant SCCs leads to tumour regression, consistent with the critical role of Sox2 expressing cells in tumour maintenance. Conditional Sox2 deletion in pre-existing skin papilloma and SCC leads to their regression and decreases their ability to be propagated upon transplantation into immunodeficient mice, supporting the essential role of Sox2 in regulating CSC functions. Transcriptional profiling of Sox2-GFP expressing CSC and upon Sox2 deletion uncovered a gene network regulated by Sox2 in primary tumour cells in vivo. Chromatin immunoprecipitation identified several direct Sox2 target genes controlling tumour stemness, survival, proliferation, adhesion, invasion, and paraneoplastic syndrome. Altogether, our study demonstrates that Sox2, by marking and regulating the functions of skin tumour initiating cells and CSCs, establishes a continuum between tumour initiation and progression in primary skin tumours. We used microarrays to profile Sox2-GFP expressing CSC to uncover a gene network regulated by Sox2 in primary tumour cells in vivo. Two different biological replicates from SOX2-GFP+ and SOX2-GFP- TECs (control) from 2 different SCC from 2 different mice were analysed. Total RNA was analysed using Mouse whole genome 430 2.0 array from Affymetrix.

Dataset Information

Gene expression in colon cancer stem cells (CSC) cultures identified by Wnt signaling levels

Publications

Wnt activity defines colon cancer stem cells and is regulated by the microenvironment.

Similar Datasets

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