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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.

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