期刊
CANCER RESEARCH
卷 70, 期 11, 页码 4460-4469出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-09-1107
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资金
- NIH [R01CA134767, R01 CA085567, R01CA113669]
- Flight Attendant Medical Research Foundation
- National Pancreas Foundation
- Sol Goldman Pancreatic Cancer Research Center
- Michael Rolfe Foundation for Pancreatic Cancer Research
- BONFOR [O-111.0001.2]
Cyclin-dependent kinase 5 (CDK5), a neuronal kinase that functions in migration, has been found to be activated in some human cancers in which it has been implicated in promoting metastasis. In this study, we investigated the role of CDK5 in pancreatic cancers in which metastatic disease is most common at diagnosis. CDK5 was widely active in pancreatic cancer cells. Functional ablation significantly inhibited invasion, migration, and anchorage-independent growth in vitro, and orthotopic tumor formation and systemic metastases in vivo. CDK5 blockade resulted in the profound inhibition of Ras signaling through its critical effectors RalA and RalB. Conversely, restoring Ral function rescued the effects of CDK5 inhibition in pancreatic cancer cells. Our findings identify CDK5 as a pharmacologically tractable target to degrade Ras signaling in pancreatic cancer. Cancer Res; 70(11); 4460-9. (C) 2010 AACR.
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