Other
14 Authors
- Kasprzak B,
- Fu XY,
- Qiao W,
- Hong S,
- Letterio JJ,
- Kim BG,
- Mamura M,
- Deng C,
- Wolfraim L,
- Mushinski E,
- Anver M,
- Li C,
- Potter M,
- Kim SJ
| First Author | Kim BG | Year | 2006 |
| Journal | Nature | Volume | 441 |
| Issue | 7096 | Pages | 1015-9 |
| PubMed ID | 16791201 | Mgi Jnum | J:110041 |
| Mgi Id | MGI:3630361 | Doi | 10.1038/nature04846 |
| Citation | Kim BG, et al. (2006) Smad4 signalling in T cells is required for suppression of gastrointestinal cancer. Nature 441(7096):1015-9 |
| abstractText | SMAD4 (MAD homologue 4 (Drosophila)), also known as DPC4 (deleted in pancreatic cancer), is a tumour suppressor gene that encodes a central mediator of transforming growth factor-beta signalling. Germline mutations in SMAD4 are found in over 50% of patients with familial juvenile polyposis, an autosomal dominant disorder characterized by predisposition to hamartomatous polyps and gastrointestinal cancer. Dense inflammatory cell infiltrates underlay grossly normal appearing, non-polypoid colonic and gastric mucosa of patients with familial juvenile polyposis. This prominent stromal component suggests that loss of SMAD4-dependent signalling in cells within the epithelial microenvironment has an important role in the evolution of intestinal tumorigenesis in this syndrome. Here we show that selective loss of Smad4-dependent signalling in T cells leads to spontaneous epithelial cancers throughout the gastrointestinal tract in mice, whereas epithelial-specific deletion of the Smad4 gene does not. Tumours arising within the colon, rectum, duodenum, stomach and oral cavity are stroma-rich with dense plasma cell infiltrates. Smad4(-/-) T cells produce abundant T(H)2-type cytokines including interleukin (IL)-5, IL-6 and IL-13, known mediators of plasma cell and stromal expansion. The results support the concept that cancer, as an outcome, reflects the loss of the normal communication between the cellular constituents of a given organ, and indicate that Smad4-deficient T cells ultimately send the wrong message to their stromal and epithelial neighbours. |
