Department of Pathology, The University of Hong Kong, China.
Histol Histopathol. 2012 Sep;27(9):1121-30. doi: 10.14670/HH-27.1121.
In recent years, much attention has been paid to the concept of cancer stem cells (CSC) and self-renewal related pathways in cancer biology. This review outlines the dysregulated stemness-related genes or transcription factors in gynecological cancers. Hedgehog (Hh) and Notch signaling are important pathways in tissue pattern programming and cell fate determination during embryonic development. Hyperactivation of these two pathways was frequently observed in gynecological malignancies such as ovarian, endometrial and cervical cancers. In contrast, the expression profiles of pluripotency-regulating core transcriptional circuitry: Nanog, Oct4 and Sox2 appear heterogeneous. Among these transcription factors, overexpression of Nanog was found to exert a prominent effect in gynecological tumorigenesis, while dysregulations of Oct4 and Sox2 may vary in a context dependent manner. On the other hand, the isolation of putative CSC illustrates a hierarchy model of tumor heterogeneity, in which only a subset of cells among biologically distinct populations can initiate tumor growth. Re-activation of these pluripotent transcription factors (Nanog, Oct4 and/or Sox2) in association with distinct tumorigenic properties could be found in clones isolated from gynecological tumors using various approaches. Recent understanding on the roles of Hh and Notch signaling in enhancing CSC survival may help to better understand the mechanism of carcinogenesis and identify new pharmaceutical targets for gynecological malignancies.
近年来，癌症生物学中癌症干细胞（CSC）和自我更新相关途径的概念引起了广泛关注。本综述概述了妇科癌症中失调的干性相关基因或转录因子。Hedgehog（Hh）和 Notch 信号通路是胚胎发育过程中组织模式编程和细胞命运决定的重要途径。这两条通路在卵巢癌、子宫内膜癌和宫颈癌等妇科恶性肿瘤中经常被过度激活。相比之下，多能性调节核心转录电路的表达谱：Nanog、Oct4 和 Sox2 表现出异质性。在这些转录因子中，Nanog 的过表达被发现对妇科肿瘤发生有显著影响，而 Oct4 和 Sox2 的失调可能以依赖于上下文的方式发生变化。另一方面，CSC 的分离说明了肿瘤异质性的层次模型，其中只有在生物学上不同的细胞亚群中才能启动肿瘤生长。使用各种方法从妇科肿瘤中分离出的克隆中，可以发现与特定肿瘤发生特性相关的这些多能转录因子（Nanog、Oct4 和/或 Sox2）的重新激活。最近对 Hh 和 Notch 信号在增强 CSC 存活中的作用的理解，有助于更好地理解致癌发生的机制，并为妇科恶性肿瘤确定新的药物靶点。
