Chen Hsiao-Fan, Wu Kou-Juey
Research Center for Tumor Medical Science, Graduate Institute of Cancer Biology, China Medical University, Taichung 404, Taiwan.
Stem Cells Int. 2016;2016:6439864. doi: 10.1155/2016/6439864. Epub 2015 Dec 28.
Tumor hypoxia is associated with malignant biological phenotype including enhanced angiogenesis and metastasis. Hypoxia increases the expression of vascular endothelial cell growth factor (VEGF), which directly participates in angiogenesis by recruiting endothelial cells into hypoxic area and stimulating their proliferation, for increasing vascular density. Recent research in tumor biology has focused on the model in which tumor-derived endothelial cells arise from tumor stem-like cells, but the detailed mechanism is not clear. Twist1, an important regulator of epithelial-mesenchymal transition (EMT), has been shown to mediate tumor metastasis and induce tumor angiogenesis. Notch signaling has been demonstrated to be an important player in vascular development and tumor angiogenesis. KLF4 (Krüppel-like factor 4) is a factor commonly used for the generation of induced pluripotent stem (iPS) cells. KLF4 also plays an important role in the differentiation of endothelial cells. Although Twist1 is known as a master regulator of mesoderm development, it is unknown whether Twist1 could be involved in endothelial transdifferentiation of tumor-derived cells. This review focuses on the role of Twist1-Jagged1/Notch-KLF4 axis on tumor-derived endothelial transdifferentiation, tumorigenesis, metastasis, and cancer stemness.
肿瘤缺氧与包括增强血管生成和转移在内的恶性生物学表型相关。缺氧会增加血管内皮细胞生长因子（VEGF）的表达，VEGF通过将内皮细胞募集到缺氧区域并刺激其增殖来直接参与血管生成，从而增加血管密度。肿瘤生物学的最新研究集中在肿瘤来源的内皮细胞源自肿瘤干细胞样细胞的模型上，但具体机制尚不清楚。Twist1是上皮-间质转化（EMT）的重要调节因子，已被证明可介导肿瘤转移并诱导肿瘤血管生成。Notch信号已被证明是血管发育和肿瘤血管生成中的重要参与者。KLF4（Krüppel样因子4）是常用于诱导多能干细胞（iPS）生成的因子。KLF4在内皮细胞分化中也起着重要作用。尽管Twist1被认为是中胚层发育的主要调节因子，但尚不清楚Twist1是否参与肿瘤来源细胞的内皮转分化。本综述重点关注Twist1-Jagged1/Notch-KLF4轴在肿瘤来源的内皮转分化、肿瘤发生、转移和癌症干性中的作用。
