| First Author | Wang Y | Year | 2013 |
| Journal | Cancer Discov | Volume | 3 |
| Issue | 3 | Pages | 294-307 |
| PubMed ID | 23274911 | Mgi Jnum | J:198246 |
| Mgi Id | MGI:5495897 | Doi | 10.1158/2159-8290.CD-12-0198 |
| Citation | Wang Y, et al. (2013) Mutant N-RAS protects colorectal cancer cells from stress-induced apoptosis and contributes to cancer development and progression. Cancer Discov 3(3):294-307 |
| abstractText | N-RAS is one member of a family of oncoproteins that are commonly mutated in cancer. Activating mutations in NRAS occur in a subset of colorectal cancers, but little is known about how the mutant protein contributes to the onset and progression of the disease. Using genetically engineered mice, we find that mutant N-RAS strongly promotes tumorigenesis in the context of inflammation. The protumorigenic nature of mutant N-RAS is related to its antiapoptotic function, which is mediated by activation of a noncanonical mitogen-activated protein kinase pathway that signals through STAT3. As a result, inhibition of MAP-ERK kinase selectively induces apoptosis in autochthonous colonic tumors expressing mutant N-RAS. The translational significance of this finding is highlighted by our observation that NRAS mutation correlates with a less favorable clinical outcome for patients with colorectal cancer. These data show for the first time the important role that N-RAS plays in colorectal cancer. |
