Yuan, T. L., Amzallag, A., Bagni, R., Yi, M., Afghani, S., Burgan, W., Fer, N., Strathern, L. A., Powell, K., Smith, B., Waters, A. M., Drubin, D., Thomson, T., Liao, R., Greninger, P., Stein, G. T., Murchie, E., Cortez, E., Egan, R. K., Procter, L., Bess, M., Cheng, K. T., Lee, C. S., Lee, L. C., Fellmann, C., Stephens, R., Luo, J., Lowe, S. W., Benes, C. H., McCormick, F. (February 2018) Differential Effector Engagement by Oncogenic KRAS. Cell Rep, 22 (7). pp. 1889-1902.
Abstract
KRAS can bind numerous effector proteins, which activate different downstream signaling events. The best known are RAF, phosphatidylinositide (PI)-3' kinase, and RalGDS families, but many additional direct and indirect effectors have been reported. We have assessed how these effectors contribute to several major phenotypes in a quantitative way, using an arrayed combinatorial siRNA screen in which we knocked down 41 KRAS effectors nodes in 92 cell lines. We show that every cell line has a unique combination of effector dependencies, but in spite of this heterogeneity, we were able to identify two major subtypes of KRAS mutant cancers of the lung, pancreas, and large intestine, which reflect different KRAS effector engagement and opportunities for therapeutic intervention.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Kras RNAi screen Rsk paralogs redundancy |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNAi bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > KRAS |
| CSHL Authors: | |
| Communities: | CSHL labs > Lowe lab |
| Depositing User: | Matt Covey |
| Date: | 13 February 2018 |
| Date Deposited: | 21 Feb 2018 15:34 |
| Last Modified: | 19 Jul 2019 18:31 |
| PMCID: | PMC6343826 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/36070 |
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