Pancreatic cancer and precursor pancreatic intraepithelial neoplasia lesions are devoid of primary cilia

E. Scott Seeley, Catherine Carrière, Tobias Goetze, Daniel S. Longnecker, Murray Korc

Research output: Contribution to journalArticle

153 Scopus citations

Abstract

Primary cilia have been proposed to participate in the modulation of growth factor signaling pathways. In this study, we determined that ciliogenesis is suppressed in both pancreatic cancer cells and pancreatic intraepithelial neoplasia (PanIN) lesions in human pancreatic ductal adenocarcinoma (PDAC). Primary cilia were absent in these cells even when not actively proliferating. Cilia were also absent from mouse PanIN cells in three different mouse models of PDAC driven by an endogenous oncogenic Kras allele. Inhibition of Kras effector pathways restored ciliogenesis in a mouse pancreatic cancer cell line, raising the possibility that cilio-genesis may be actively repressed by oncogenic Kras. By contrast, normal duct, islet, and centroacinar cells retained primary cilia in both human and mouse pancreata. Thus, arrested ciliogenesis is a cardinal feature of PDAC and its precursor PanIN lesions, does not require ongoing proliferation, and could potentially be targeted pharmacologically.

Original languageEnglish (US)
Pages (from-to)422-430
Number of pages9
JournalCancer Research
Volume69
Issue number2
DOIs
StatePublished - Jan 15 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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