CUB domain-containing protein 1, a prognostic factor for human pancreatic cancers, promotes cell migration and extracellular matrix degradation

Yuri Miyazawa, Takamasa Uekita, Nobuyoshi Hiraoka, Satoko Fujii, Tomoo Kosuge, Yae Kanai, Yoshihisa Nojima, Ryuichi Sakai

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

CUB domain-containing protein 1 (CDCP1) is a membrane protein that is highly expressed in several solid cancers. We reported previously that CDCP1 regulates anoikis resistance as well as cancer cell migration and invasion, although the underlying mechanisms have not been elucidated. In this study, we found that expression of CDCP1 in pancreatic cancer tissue was significantly correlated with overall survival and that CDCP1 expression in pancreatic cancer cell lines was relatively high among solid tumor cell lines. Reduction of CDCP1 expression in these cells suppressed extracellular matrix (ECM) degradation by inhibiting matrix metalloproteinase-9 secretion. Using the Y734F mutant of CDCP1, which lacks the tyrosine phosphorylation site, we showed that CDCP1 regulates cell migration, invasion, and ECM degradation in a tyrosine phosphorylation-dependent manner and that these CDCP1-associated characteristics were inhibited by blocking the association of CDCP1 and protein kinase Cδ (PKCδ). CDCP1 modulates the enzymatic activity of PKCδ through the tyrosine phosphorylation of PKCδ by recruiting PKCδ to Src family kinases. Cortactin, which was detected as a CDCP1-dependent binding partner of PKCδ, played a significant role in migration and invasion but not in ECM degradation of pancreatic cells. These results suggest that CDCP1 expression might play a crucial role in poor outcome of pancreatic cancer through promotion of invasion and metastasis and that molecules blocking the expression, phosphorylation, or the PKCδ-binding site of CDCP1 are potential therapeutic candidates.

Original languageEnglish
Pages (from-to)5136-5146
Number of pages11
JournalCancer Research
Volume70
Issue number12
DOIs
Publication statusPublished - 2010 Jun 15

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'CUB domain-containing protein 1, a prognostic factor for human pancreatic cancers, promotes cell migration and extracellular matrix degradation'. Together they form a unique fingerprint.

  • Cite this