Autocrine IGF1 Signaling Mediates Pancreatic Tumor Cell Dormancy in the Absence of Oncogenic Drivers

Nirakar Rajbhandari, Wan chi Lin, Barbara L. Wehde, Aleata A. Triplett, Kay Uwe Wagner

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Mutant KRAS and c-MYC are oncogenic drivers and rational therapeutic targets for the treatment of pancreatic cancer. Although tumor growth and homeostasis are largely dependent on these oncogenes, a few residual cancer cells are able to survive the ablation of mutant KRAS and c-MYC. By performing a genome-wide gene expression analysis of in vivo-derived bulk tumor cells and residual cancer cells lacking the expression of mutant KRAS or c-MYC, we have identified an increase in autocrine IGF1/AKT signaling as a common survival mechanism in dormant cancer cells. The pharmacological inhibition of IGF-1R reduces residual disease burden and cancer recurrence, suggesting that this molecular pathway is crucial for the survival of cancer cells in the absence of the primary oncogenic drivers.

Original languageEnglish (US)
Pages (from-to)2243-2255
Number of pages13
JournalCell Reports
Volume18
Issue number9
DOIs
StatePublished - Feb 28 2017

Keywords

  • AKT
  • IGF1 signaling
  • KRAS
  • c-MYC
  • cancer dormancy
  • genetic engineering
  • mouse models
  • oncogenes
  • pancreatic cancer

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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