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| Status |
Public on Sep 01, 2020 |
| Title |
FGF Signaling in the Self-Renewal of Colon Cancer Organoids |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
With their ability to self-renew and simultaneously fuel the bulk tumor mass with highly proliferative tumor cells, cancer stem cells (CSC) are supposedly driving cancer progression. However, the CSC-phenotype in colorectal cancer (CRC) is unstable and dependent on environmental cues. Since FGF2 is essential for adult and embryonic stem cell culture to maintain self-renewal, we investigated its role in advanced CRC using tumor-derived organoids as experimental model. We found that FGF-Receptor (FGFR) inhibition prevents organoid formation in very early expanding cells but induces cyst formation when applied to already established organoids. Comprehensive transcriptome analyses revealed that the induction of the transcription factor activator protein-1 (AP-1) together with a MAPK stimulation was most prominent after FGFR-inhibition. These effects resemble mechanisms of an acquired resistance against other described tyrosine kinase inhibitors such as targeted therapies against the EGF-Receptor. Furthermore, we detected elevated expression levels of several self-renewal and stemness-associated genes in organoid cultures with active FGF2 signaling. The combined data assumes that CSC are a heterogeneous subpopulation while self-renewal is a common feature regulated by many different pathways. Finally, we highlight the effects of FGF2 signaling as one of numerous aspects of the complex regulation of stemness in cancer.
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| Overall design |
The transcriptomes of colon cancer organoids with and without FGFR inhibition and human ESC lines were compared by microarray analysis (PrimeView Human Gene Expression Array, Affymetrix, Thermo Fisher Scientific).
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| Contributor(s) |
Wruck W, Otte J, Adjaye J |
| Citation(s) |
31758153 |
| |
| Submission date |
Aug 22, 2018 |
| Last update date |
Dec 01, 2020 |
| Contact name |
Wasco Wruck |
| E-mail(s) |
wasco.wruck@med.uni-duesseldorf.de
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| Organization name |
Universitätsklinikum Düsseldorf
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| Street address |
Moorenstr. 5
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| City |
Düsseldorf |
| ZIP/Postal code |
40225 |
| Country |
Germany |
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| Platforms (1) |
| GPL16043 |
GeneChip® PrimeView™ Human Gene Expression Array (with External spike-in RNAs) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA487466 |
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