Daley G Q
Division of Pediatric Hematology and Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cold Spring Harb Symp Quant Biol. 2008;73:171-4. doi: 10.1101/sqb.2008.73.041. Epub 2009 Jan 15.
With its hallmarks of unregulated cell proliferation and compromised differentiation, cancer represents a derangement of normal tissue homeostasis. A common set of pathways are activated in the transformed state, through either mutation or altered epigenetic regulation, and both heritable effects sustain the tumor. Classical views of cancer have invoked tissue dedifferentiation in the oncogenic process, whereas modern views embodied in the cancer stem cell hypothesis hold that cancer emerges from primitive tissue stem cells or specific progenitor populations that through mutations assume the self-renewal properties of stem cells. Recently, somatic tissues have been reprogrammed to a pluripotent state resembling embryonic stem (ES) cells by ectopic expression of a cocktail of transcription factors. The factors that drive reprogramming are oncogenes or have been linked to cellular transformation, suggesting that tumorigenesis and somatic cell reprogramming might indeed share common mechanisms of dedifferentiation.
癌症具有不受调控的细胞增殖和分化受损的特征,代表了正常组织稳态的紊乱。通过突变或表观遗传调控改变,一组常见的信号通路在转化状态下被激活,并且这两种可遗传效应维持肿瘤生长。癌症的传统观点认为在致癌过程中会发生组织去分化,而癌症干细胞假说所体现的现代观点则认为癌症起源于原始组织干细胞或特定祖细胞群体,这些细胞通过突变获得了干细胞的自我更新特性。最近,通过异位表达一组转录因子,体细胞已被重编程为类似于胚胎干细胞(ES细胞)的多能状态。驱动重编程的因子是癌基因或已与细胞转化相关联,这表明肿瘤发生和体细胞重编程可能确实共享去分化的共同机制。