Department of Biomedical Genetics, University of Rochester, Rochester, NY 14642, USA.
Cell Stem Cell. 2013 Mar 7;12(3):304-15. doi: 10.1016/j.stem.2013.01.007.
Sox2 regulates the self-renewal of multiple types of stem cells. Recent studies suggest it also plays oncogenic roles in the formation of squamous carcinoma in several organs, including the esophagus where Sox2 is predominantly expressed in the basal progenitor cells of the stratified epithelium. Here, we use mouse genetic models to reveal a mechanism by which Sox2 cooperates with microenvironmental signals to malignantly transform epithelial progenitor cells. Conditional overexpression of Sox2 in basal cells expands the progenitor population in both the esophagus and forestomach. Significantly, carcinoma only develops in the forestomach, where pathological progression correlates with inflammation and nuclear localization of Stat3 in progenitor cells. Importantly, co-overexpression of Sox2 and activated Stat3 (Stat3C) also transforms esophageal basal cells but not the differentiated suprabasal cells. These findings indicate that basal stem/progenitor cells are the cells of origin of squamous carcinoma and that cooperation between Sox2 and microenvironment-activated Stat3 is required for Sox2-driven tumorigenesis.
Sox2 调节多种类型干细胞的自我更新。最近的研究表明，它在包括食管在内的几个器官的鳞状细胞癌形成中也发挥致癌作用，在食管中 Sox2 主要在分层上皮的基底祖细胞中表达。在这里，我们使用小鼠遗传模型揭示了 Sox2 与微环境信号合作使上皮祖细胞恶性转化的机制。Sox2 在基底细胞中的条件过表达可在食管和前胃中均扩大祖细胞群体。重要的是，癌仅在前胃中发展，在前胃中，病理进展与祖细胞中 Stat3 的炎症和核定位相关。重要的是，Sox2 和激活的 Stat3（Stat3C）的共过表达也可转化食管基底细胞，但不能转化分化的上基细胞。这些发现表明基底干细胞/祖细胞是鳞状细胞癌的起源细胞，Sox2 与微环境激活的 Stat3 之间的合作是 Sox2 驱动的肿瘤发生所必需的。
