ID1 and ID3 Regulate the Self-Renewal Capacity of聽Human Colon Cancer-Initiating Cells through p21

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• 作者：Catherine  ; A. O'Brien¹ ; ² ; ³ ; ⁷ ; ^{cobrien@uhnres.utoronto.ca} ; Antonija Kreso¹ ; ⁴ ; ⁷ ; Paul Ryan⁵ ; Karin  ; G. Hermans¹ ; Lianne Gibson¹ ; Yadong Wang¹ ; Andrew Tsatsanis¹ ; Steven Gallinger² ; ⁶ ; John  ; E. Dick¹ ; ⁴ ; ^{jdick@uhnres.utoronto.ca}
• 刊名：Cancer Cell
• 出版年：2012
• 期刊代码：43_15356108
• 类别：med
• 出版时间：12 June, 2012
• 卷：21
• 期：6
• 页码：777-792
• 文件大小：2129 K

摘要

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Summary

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.