Asymmetric Division Gene Neurl2 Mediates Twist2 Regulation of Self-Renewal of Mouse Lewis Lung Cancer Stem Cells

Cancer stem cells (CSCs) play an important role in tumor development. While Epithelial-Mesenchymal Transition (EMT) has been shown to promote CSC self-renewal, underlying mechanisms are unclear. Here we identified and characterized the requirement of twist2, the EMT transcription factor, for the regulation of self-renewal thus stemness of mouse Lewis lung CSCs both in vitro and in vivo. Further, we elucidated the role of neurl2, an asymmetric division gene for normal stem cells, in mediating the self-renewal promoting activity of twist2. Moreover, analysis of TCGA showed a positive correlation between the expression of twist2 and the development of lung adenocarcinoma, and a negative correlation between neurl2 and lung adenocarcinoma development. In summary, our study provides a new mechanistic insight of regulation of CSC self-renewal by EMT.