The emerging roles of Oct4 in tumor-initiating cells.
The emerging roles of Oct4 in tumor-initiating cells.
复制标题
DOI：
10.1152/ajpcell.00212.2015
复制
发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Ying-Jie Wang;M. Herlyn
中科院分区：
文献类型：
--
作者：
Ying-Jie Wang;M. Herlyn
八聚体结合转录因子4（Oct 4）是一种同源结构域转录因子，被公认为控制多能干细胞自我更新和多能性的主因子。此外，大量的研究已经记录了在肿瘤细胞和组织中检测到Oct 4，并表明其在未分化的肿瘤起始细胞（TIC）亚群中的富集，这些细胞是肿瘤起始、转移和对抗癌疗法的抗性的关键原因。有间接证据表明Oct 4在癌细胞和TIC中的低水平表达，并且大量基于Oct 4敲低和过表达的研究涉及Oct 4参与各种TIC功能，如其自我更新和存活、上皮-间质转化（EMT）和转移以及耐药性发展。在一些研究中，已经努力在不同来源的TIC中鉴定Oct 4靶基因。基于这些信息，TIC中的Oct 4似乎通过与多能干细胞中的机制完全不同的机制起作用，未来研究的主要挑战是解开Oct 4作用的分子机制，特别是解决关于如此低水平的Oct 4如何在TIC中发挥其功能的问题。从其天然微环境中获得足够高数量和纯度的细胞是可靠分析TIC中Oct 4功能及其靶基因的关键，所获得的信息可以极大地促进靶向和根除这些细胞。
Octamer-binding transcription factor 4 (Oct4), a homeodomain transcription factor, is well established as a master factor controlling the self-renewal and pluripotency of pluripotent stem cells. Also, a large body of research has documented the detection of Oct4 in tumor cells and tissues and has indicated its enrichment in a subpopulation of undifferentiated tumor-initiating cells (TICs) that critically account for tumor initiation, metastasis, and resistance to anticancer therapies. There is circumstantial evidence for low-level expression of Oct4 in cancer cells and TICs, and the participation of Oct4 in various TIC functions such as its self-renewal and survival, epithelial-mesenchymal transition (EMT) and metastasis, and drug resistance development is implicated from considerable Oct4 knockdown and overexpression-based studies. In a few studies, efforts have been made to identify Oct4 target genes in TICs of different sources. Based on such information, Oct4 in TICs appears to act via mechanisms quite distinct from those in pluripotent stem cells, and a main challenge for future studies is to unravel the molecular mechanisms of action of Oct4, particularly to address the question on how such low levels of Oct4 may exert its functions in TICs. Acquiring cells from their native microenvironment that are of high enough quantity and purity is the key to reliably analyze Oct4 functions and its target genes in TICs, and the information gained may greatly facilitate targeting and eradicating those cells.