In the TME, CSCs could transdifferentiate into cells (such as TECs) that differ from their own original lineage along the axis of Twist1-Notch-KLF4 [7] or differentiate into their original lineage of tumor cell progeny, of which the latter differentiation process is bidirectional, meaning that the differentiated tumor cells can conversely dedifferentiate into CSCs. This evidence concerns the gene KLF4 and neoplasm.