6月12日,，Cancer Cell雜志報道了結腸癌腫瘤起始細胞自我更新性調節(jié)機制的最新進展。
越來越多的證據(jù)表明,，某些腫瘤內部是分等級,，分層次組織起來的。其中,，有一群稱為腫瘤起始細胞（C-ICs）的相對稀有細胞起著維持整個腫瘤群落的作用,。雖然，已知在連續(xù)的移植情況下仍可形成新的腫瘤是C-ICs的一個重要特征,，但這個過程的控制基因卻一直不明,。
本研究發(fā)現(xiàn)，DNA結合抑制子1（ID1）和DNA結合抑制子3（ID3）基因共同作用，通過細胞周期抑制子p21限制細胞周期,，來控制結腸癌C-ICs的自我更新,。通過ID1和ID3調節(jié)p21是防止過度DNA損傷積累和繼之的結腸癌C-ICs功能性耗盡的核心機制。
此外,，ID1和ID3沉默可增加結腸癌C-ICs對化學治療試劑奧沙利鉑的敏感性,。這提示，腫瘤起始功能是與化療抗性相聯(lián)系的,。（生物谷bioon.com）
doi:10.1016/j.cell.2011.10.017
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PMID:
ID1 and ID3 Regulate the Self-Renewal Capacity of Human Colon Cancer-Initiating Cells through p21
Catherine A. O'Brien, Antonija Kreso, Paul Ryan, Karin G. Hermans, Lianne Gibson, Yadong Wang, et al
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.
