Inhibiting the cyclin-dependent kinase CDK5 blocks pancreatic cancer formation and progression through the suppression of Ras-Ral signaling

Georg Feldmann, Anjali Mishra, Seung Mo Hong, Savita Bisht, Christopher J. Strock, Douglas W. Ball, Michael Goggins, Anirban Maitra, Barry D. Nelkin

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4460-4469
Number of pages10
JournalCancer Research
Volume70
Issue number11
DOIs
StatePublished - Jun 1 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Inhibiting the cyclin-dependent kinase CDK5 blocks pancreatic cancer formation and progression through the suppression of Ras-Ral signaling'. Together they form a unique fingerprint.

Cite this