ID1 and ID3 Regulate the Self-Renewal Capacity of Human Colon Cancer-Initiating Cells through p21
ID1 and ID3 Regulate the Self-Renewal Capacity of Human Colon Cancer-Initiating Cells through p21
复制标题
DOI：
10.1016/j.ccr.2012.04.036
复制
发表时间：
2012-06-12
期刊：
影响因子：
50.3
通讯作者：
Dick, John E.
中科院分区：
文献类型：
--
作者：
O'Brien, Catherine A.;Kreso, Antonija;Dick, John E.
越来越多的证据表明，一些癌症是有等级组织的，由相对罕见的致癌细胞（c - ic）维持。尽管在连续移植中启动肿瘤的能力是所有c - ic的一个标志，但对控制这一过程的基因知之甚少。在这里，我们建立了ID1和ID3共同作用，通过细胞周期抑制剂p21驱动的细胞周期限制来控制结肠癌启动细胞（CC-IC）的自我更新。ID1和ID3对p21的调控是防止过量DNA损伤积累和随后cc - ic功能衰竭的主要机制。此外，ID1和ID3的沉默增加了CC-ICs对化疗药物奥沙利铂的敏感性，将肿瘤起始功能与化疗耐药性联系起来。
There is increasing evidence that some cancers are hierarchically organized, sustained by a relatively rare population of cancer-initiating cells (C-ICs). Although the capacity to initiate tumors upon serial transplantation is a hallmark of all C-ICs, little is known about the genes that control this process. Here, we establish that ID1 and ID3 function together to govern colon cancer-initiating cell (CC-IC) self-renewal through cell-cycle restriction driven by the cell-cycle inhibitor p21. Regulation of p21 by ID1 and ID3 is a central mechanism preventing the accumulation of excess DNA damage and subsequent functional exhaustion of CC-ICs. Additionally, silencing of ID1 and ID3 increases sensitivity of CC-ICs to the chemotherapeutic agent oxaliplatin, linking tumor initiation function with chemotherapy resistance.