ReferenceID 3522
K-Ras Promotes Tumorigenicity through Suppression of Non-canonical Wnt Signaling
Cell
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. Her
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Record Fields
Scalar fields from the final reference record.
- Reference Id
- 3522
- Evidence Id
- 20112
- Core Evidence Id
- 20112
- Source Reference Id
- 350
- Herb2 Reference Id
- HBREF000641
- Subject Paper Key
- HBIN040889_26590425
- Pubmed Id
- 26590425
- Doi
- 10.1016/j.cell.2015.10.041
- Paper Title
- K-Ras Promotes Tumorigenicity through Suppression of Non-canonical Wnt Signaling
- Paper 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(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.
- Journal
- Cell
- Publish Year
- 2015
- Experiment Subject
- k-ras mutant pancreatic cancer cells
- Experiment Type
- Cell Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- K-Ras Promotes Tumorigenicity through Suppression of Non-canonical Wnt Signaling
- Bilingual Status
- semi_complete