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Series GSE84588 Query DataSets for GSE84588
Status Public on Jul 14, 2019
Title Notch1 enhances NF-κB activation to promote CD133+ Skin Cancer Stem Cells
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Cancer stem-like cells are hypothesized to be the major tumor initiating cell (TIC) population of human cutaneous squamous cell carcinoma (hcSCC), but the molecular alterations underpinning their cellular phenotype remain undefined. Here, a small CD133+CD31-CD45-CD61-CD24- (CD133+) cell population enriched for self-renewing and TIC features was isolated by sorting from primary hcSCC tumors. CD133+ cells show enhanced spheroid formation in vitro and tumor generation in vivo. Gene expression profiling comparing CD133+ with CD133- cells revealed that CD133+ cells expressed enriched stem cell-like and cancer-related gene signatures. Eighty differentially expressed stem cell-related genes were identified in CD133+ cells, where the top pathways include Notch, Notch1-mediated NF-κB, and WNT signaling. Overexpression of growth factor receptors, PI3K/mTOR, and STAT pathway genes and inactivation of genes regulating epigenetic modification of chromatin implicated in cancer were also identified. Verification of these gene signatures was conducted with Nanostring in an independent tumor set. Pharmacologic or genetic modulation of Notch1, IKKα, RELA and RELB modulated NF-κB transactivation, the CD133+ population, and phenotype. Immunofluorescent staining confirmed co-localization of CD133+ and IKKα expression in SCC tumor specimens. Our data support the linkage and importance of non-canonical Notch1 and IKK-mediated NF-κB activation in promoting CD133+ population and TIC phenotype in hcSCC.
Overall design Comparing Gene expression profiling for CD133+ with CD133- cells from the sorting from primary hcSCC tumors by 15 samples for both positive and neg in total 30 samples.
Contributor(s) Quan XX, Voong N, Chen W, Coupar J, Lee S, Petersen DW, Edelman DC, Meltzer PS, Montemarano A, Braun M, Vogel J, Chen Z, Van Waes C
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Submission date Jul 19, 2016
Last update date Jul 15, 2019
Contact name WeiPing Chen
Phone 301-496-0175
Organization name NIDDK/NIH
Department GCL
Lab Genomics Core Lab
Street address Bldg 8, Room 1A11, NIDDK/NIH
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (1)
GPL6244 [HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version]
Samples (30)
GSM2242210 S100 neg
GSM2242211 S100 pos
GSM2242212 S104 neg
BioProject PRJNA330392

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE84588_RAW.tar 111.1 Mb (http)(custom) TAR (of CEL)
GSE84588_RMA_data_gene_level.txt.gz 453.6 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data provided as supplementary file
Processed data included within Sample table
Processed data is available on Series record

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