Cancer stem cells: a shifting subpopulation of cells with stemness?

Carcinogenesis and tumor cells had long been thought to be produced by genetic mutations, until the emergence of the cancer stem cell (CSC) model. This relatively new model reveals another layer of complexity in malignancy formation and maintenance. However, these hard-to-track subpopulations have not only been challenging to understand at the molecular level but have also prevented the development of novel CSC-based cancer therapies. Accumulating evidence from previous studies has suggested that CSCs might be derived from either somatic stem cells (SCCs) or differentiated progenitor cells and that they constantly reestablish their niches; these factors underlie the variability in their frequencies and biological marker expression. Therefore, we present the hypothesis that CSCs possess constantly evolving features. During tumorigenesis, the characteristics of the CSCs may change, thus presenting a "moving target". We also suggest that a multifaceted, integrated strategy combining traditional cell surface markers and transcriptional factor targeting methods to identify "stemness" should lead to the better isolation and characterization of CSCs. Corresponding laboratory approaches to test this hypothesis are also provided.