Figure 1.

The CSC phenotype is dynamic and encompasses molecular changes that alter “stemness." This process is influenced by autocrine and paracrine pathways including environmental cues that modify the DNA methylation landscape and histone marks, regulate non-coding RNAs, and modulate the expression of transcription factors, all leading to fate-determining gene expression changes. De-differentiation and acquisition of stem cell qualities results in tumor cells with self-renewal capability, tumor-propagating capacity, and treatment resistance.