| First Author | Wang MT | Year | 2015 |
| Journal | Cell | Volume | 163 |
| Issue | 5 | Pages | 1237-1251 |
| PubMed ID | 26590425 | Mgi Jnum | J:228018 |
| Mgi Id | MGI:5704264 | Doi | 10.1016/j.cell.2015.10.041 |
| Citation | Wang MT, et al. (2015) K-Ras Promotes Tumorigenicity through Suppression of Non-canonical Wnt Signaling. Cell 163(5):1237-51 |
| abstractText | K-Ras and H-Ras share identical effectors and have similar properties; however, the high degree of tumor-type specificity associated with K-Ras and H-Ras mutations suggests that they have unique roles in oncogenesis. Here, we report that oncogenic K-Ras, but not H-Ras, suppresses non-canonical Wnt/Ca(2+) signaling, an effect that contributes strongly to its tumorigenic properties. K-Ras does this by binding to calmodulin and so reducing CaMKii activity and expression of Fzd8. Restoring Fzd8 in K-Ras mutant pancreatic cells suppresses malignancy, whereas depletion of Fzd8 in H-Ras(V12)-transformed cells enhances their tumor initiating capacity. Interrupting K-Ras-calmodulin binding using genetic means or by treatment with an orally active protein kinase C (PKC)-activator, prostratin, represses tumorigenesis in K-Ras mutant pancreatic cancer cells. These findings provide an alternative way to selectively target this "undruggable" protein. |
