Colon cancer stem cells: Controversies and perspectives

Table 1 Summary of characteristics and controversies about colon cancer stem cells

Origin	“Bottom-up” theory[30-32,34,35]
	“Top-down” theory[33]
	CSCs can derive from epithelial non-stem cells that re-express stem cell markers[36]
	CSCs can derive from bone marrow cells[37-43]
Identification assays	Serial transplantation in immune-compromised mice[8,9,27]
	Expression of cell surface marker CD133[5,8,9,14,31,44-46,48,49]
	Side Population[52-61]
Therapeutic strategies	Induction of CSC differentiation by salinomycin or BMP4[72,73]
	Monoclonal antibodies directed against cell surface molecules, such as CD133, CD44, EGFR (cetuximab) and VEGF (bevacizumab)[74,76-79]
	Blockage of self-renewal pathways, including Wnt, Notch, PTEN, Hedgehog , EMT and IL-4 pathway by microRNA or selected small-molecule antagonists[65-70,80-86]
	Target the Warburg effect[87,88]

CSC: Colon cancer stem cell; EGFR: Epidermal growth factor receptor; VEGF: Vascular endothelial growth factor; EMT: Epithelial-to-mesenchymal transition.