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

研究成果: Article査読

91 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)5136-5146
ページ数11
ジャーナルCancer Research
70
12
DOI
出版ステータスPublished - 2010 6 15
外部発表はい

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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