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Cancer Cell. 2012 Jun 12;21(6):777-92. doi: 10.1016/j.ccr.2012.04.036.

ID1 and ID3 regulate the self-renewal capacity of human colon cancer-initiating cells through p21.

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Campbell Family Institute, Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario M5G 1L7, Canada.


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.

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