부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2015.10.041 Byline: Man-Tzu Wang, Matthew Holderfield, Jacqueline Galeas, Reyno Delrosario, Minh D. To, Allan Balmain, Frank McCormick Abstract: 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.sup.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.sup.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. Author Affiliation: (1) Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, 1450 3.sup.rd Street, San Francisco, CA 94158, USA Article History: Received 12 August 2015; Revised 1 October 2015; Accepted 13 October 2015 Article Note: (miscellaneous) Published: November 19, 2015