دورية أكاديمية
Synthetic Lethal Interaction between Oncogenic KRAS Dependency and STK33 Suppression in Human Cancer Cells
| العنوان: | Synthetic Lethal Interaction between Oncogenic KRAS Dependency and STK33 Suppression in Human Cancer Cells |
|---|---|
| المؤلفون: | Scholl, Claudia, Frohling, Stefan, Dunn, Ian F., Schinzel, Anna C., Barbie, David A., Kim, So Young, Silver, Serena J., Tamayo, Pablo, Wadlow, Raymond C., Ramaswamy, Sridhar, Dohner, Konstanze, Bullinger, Lars, Sandy, Peter, Boehm, Jesse S., Root, David E., Hahn, William C., Gilliland, D. Gary, Jacks, Tyler E |
| المساهمون: | Koch Institute for Integrative Cancer Research at MIT, Sandy, Peter, Jacks, Tyler E. |
| المصدر: | Elsevier |
| بيانات النشر: | Elsevier B.V. |
| سنة النشر: | 2009 |
| المجموعة: | DSpace@MIT (Massachusetts Institute of Technology) |
| الوصف: | An alternative to therapeutic targeting of oncogenes is to perform “synthetic lethality” screens for genes that are essential only in the context of specific cancer-causing mutations. We used high-throughput RNA interference (RNAi) to identify synthetic lethal interactions in cancer cells harboring mutant KRAS, the most commonly mutated human oncogene. We find that cells that are dependent on mutant KRAS exhibit sensitivity to suppression of the serine/threonine kinase STK33 irrespective of tissue origin, whereas STK33 is not required by KRAS-independent cells. STK33 promotes cancer cell viability in a kinase activity-dependent manner by regulating the suppression of mitochondrial apoptosis mediated through S6K1-induced inactivation of the death agonist BAD selectively in mutant KRAS-dependent cells. These observations identify STK33 as a target for treatment of mutant KRAS-driven cancers and demonstrate the potential of RNAi screens for discovering functional dependencies created by oncogenic mutations that may enable therapeutic intervention for cancers with “undruggable” genetic alterations. ; National Institutes of Health (U.S.) (grant R33 CA128625) ; National Institutes of Health (U.S.) (grant NIH U54 CA112962) ; National Institutes of Health (U.S.) (grant P01 CA095616) ; National Institutes of Health (U.S.) (grant P01 CA66996) ; Starr Cancer Consortium ; Doris Duke Charitable Foundation ; MPN Research Foundation ; Deutsche Forschungsgemeinschaft (grant SCHO 1215/1-1) ; Deutsche Forschungsgemeinschaft (grant FR 2113/1-1) ; Brain Science Foundation ; Leukemia & Lymphoma Society of America |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 00928674 1097-4172 |
| العلاقة: | http://dx.doi.org/10.1016/j.cell.2009.03.017Test; Cell; http://hdl.handle.net/1721.1/96267Test; Scholl, Claudia, Stefan Fröhling, Ian F. Dunn, Anna C. Schinzel, David A. Barbie, So Young Kim, Serena J. Silver, et al. “Synthetic Lethal Interaction Between Oncogenic KRAS Dependency and STK33 Suppression in Human Cancer Cells.” Cell 137, no. 5 (May 2009): 821–834. © 2009 Elsevier Inc.; orcid:0000-0001-5785-8911 |
| الإتاحة: | https://doi.org/10.1016/j.cell.2009.03.017Test http://hdl.handle.net/1721.1/96267Test |
| حقوق: | Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. |
| رقم الانضمام: | edsbas.3C318886 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00928674 10974172 |
|---|