| First Author | Castets M | Year | 2011 |
| Journal | Nature | Volume | 482 |
| Issue | 7386 | Pages | 534-7 |
| PubMed ID | 22158121 | Mgi Jnum | J:181517 |
| Mgi Id | MGI:5311541 | Doi | 10.1038/nature10708 |
| Citation | Castets M, et al. (2012) DCC constrains tumour progression via its dependence receptor activity. Nature 482(7386):534-7 |
| abstractText | The role of deleted in colorectal carcinoma (DCC) as a tumour suppressor has been a matter of debate for the past 15 years. DCC gene expression is lost or markedly reduced in the majority of advanced colorectal cancers and, by functioning as a dependence receptor, DCC has been shown to induce apoptosis unless engaged by its ligand, netrin-1 (ref. 2). However, so far no animal model has supported the view that the DCC loss-of-function is causally implicated as predisposing to aggressive cancer development. To investigate the role of DCC-induced apoptosis in the control of tumour progression, here we created a mouse model in which the pro-apoptotic activity of DCC is genetically silenced. Although the loss of DCC-induced apoptosis in this mouse model is not associated with a major disorganization of the intestines, it leads to spontaneous intestinal neoplasia at a relatively low frequency. Loss of DCC-induced apoptosis is also associated with an increase in the number and aggressiveness of intestinal tumours in a predisposing APC mutant context, resulting in the development of highly invasive adenocarcinomas. These results demonstrate that DCC functions as a tumour suppressor via its ability to trigger tumour cell apoptosis. |
