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.

癌症干细胞（CSCs）在肿瘤发展中起重要作用。虽然上皮 - 间质转化（EMT）已被证明可促进癌症干细胞的自我更新，但其潜在机制尚不清楚。在此，我们在体外和体内鉴定并描述了EMT转录因子twist2对小鼠Lewis肺癌癌症干细胞自我更新及干性调节的需求。此外，我们阐明了正常干细胞的不对称分裂基因neurl2在介导twist2的自我更新促进活性中的作用。而且，对癌症基因组图谱（TCGA）的分析表明，twist2的表达与肺腺癌的发展呈正相关，而neurl2与肺腺癌的发展呈负相关。总之，我们的研究为EMT对癌症干细胞自我更新的调节提供了新的机制性见解。