Cancer stemness in Apc- vs. Apc/KRAS-driven intestinal tumorigenesis.
- Mehrnaz Ghazvini
- Petra Sonneveld
- Andreas Kremer
- Patrick Franken
- Andrea Sacchetti
- Yaser Atlasi
- Sabrina Roth
- Rosalie Joosten
- Ron Smits
- Riccardo Fodde
DOIAbstract
Constitutive activation of the Wnt pathway leads to adenoma formation, an obligatory step towards intestinal cancer. In view of the established role of Wnt in regulating stemness, we attempted the isolation of cancer stem cells (CSCs) from Apc- and Apc/KRAS-mutant intestinal tumours. Whereas CSCs are present in Apc/KRAS tumours, they appear to be very rare (<10(-6)) in the Apc-mutant adenomas. In contrast, the Lin(-)CD24(hi)CD29(+) subpopulation of adenocarcinoma cells appear to be enriched in CSCs with increased levels of active β-catenin. Expression profiling analysis of the CSC-enriched subpopulation confirmed their enhanced Wnt activity and revealed additional differential expression of other signalling pathways, growth factor binding p...
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