Collagen I promotes metastasis in pancreatic cancer by activating c-Jun NH2-terminal kinase 1 and up-regulating N-cadherin expression

Yasushi Shintani, Michael A. Hollingsworth, Margaret J. Wheelock, Keith R. Johnson

Research output: Contribution to journalArticle

156 Scopus citations

Abstract

We have previously shown that N-cadherin expression is associated with tumor invasion, and that some cancer cells respond to specific extracellular matrix molecules by up-regulating N-cadherin. Pancreatic cancer is characterized by excessive deposition of type I collagen. Here, we show that human pancreatic cancer cells respond to collagen I, but not other matrices, by increasing motility and up-regulating mesenchymal markers, including N-cadherin. Both collagen I-mediated motility and metastasis in a mouse model for pancreatic cancer were inhibited by N-cadherin knockdown. Furthermore, inhibiting c-Jun NH2-terminal kinase (JNK) with chemical inhibitors or short hairpin RNA abrogated all collagen I-induced changes. We show that JNK1 is activated in response to collagen I, which increases tumorigenesis by up-regulating N-cadherin expression and by increasing motility.

Original languageEnglish (US)
Pages (from-to)11745-11753
Number of pages9
JournalCancer Research
Volume66
Issue number24
DOIs
StatePublished - Dec 15 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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