Abstract：
:Despite the prevalence of KRAS mutations in human cancers, there remain no targeted therapies for treatment. The serine-threonine kinase STK33 has been proposed to be required for the survival of mutant KRAS-dependent cell lines, suggesting that small molecule kinase inhibitors of STK33 may be useful to treat KRAS-dependent tumors. In this study, we investigated the role of STK33 in mutant KRAS human cancer cells using RNA interference, dominant mutant overexpression, and small molecule inhibitors. As expected, KRAS downregulation decreased the survival of KRAS-dependent cells. In contrast, STK33 downregulation or dominant mutant overexpression had no effect on KRAS signaling or survival of these cells. Similarly, a synthetic lethal siRNA screen conducted in a broad panel of KRAS wild-type or mutant cells identified KRAS but not STK33 as essential for survival. We also obtained similar negative results using small molecule inhibitors of the STK33 kinase identified by high-throughput screening. Taken together, our findings refute earlier proposals that STK33 inhibition may be a useful therapeutic approach to target human KRAS mutant tumors.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Babij C,Zhang Y,Kurzeja RJ,Munzli A,Shehabeldin A,Fernando M,Quon K,Kassner PD,Ruefli-Brasse AA,Watson VJ,Fajardo F,Jackson A,Zondlo J,Sun Y,Ellison AR,Plewa CA,San MT,Robinson J,McCarter J,Schwandner R,Judd T,Cdoi
10.1158/0008-5472.CAN-11-0778subject
Has Abstractpub_date
2011-09-01 00:00:00pages
5818-26issue
17eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-11-0778journal_volume
71pub_type
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