Adenylate cyclase-associated protein 1 overexpressed in pancreatic cancers is involved in cancer cell motility

Ken Yamazaki, Masaaki Takamura, Yohei Masugi, Taisuke Mori, Wenlin Du, Taizo Hibi, Nobuyoshi Hiraoka, Tsutomu Ohta, Misao Ohki, Setsuo Hirohashi, Michiie Sakamoto

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Pancreatic cancer has the worst prognosis among cancers due to the difficulty of early diagnosis and its aggressive behavior. To characterize the aggressiveness of pancreatic cancers on gene expression, pancreatic cancer xenografts transplanted into severe combined immunodeficient mice served as a panel for gene-expression profiling. As a result of profiling, the adenylate cyclase-associated protein 1 (CAP1) gene was shown to be overexpressed in all of the xenografts. The expression of CAP1 protein in all 73 cases of pancreatic cancer was recognized by immunohistochemical analyses. The ratio of CAP1-positive tumor cells in clinical specimens was correlated with the presence of lymph node metastasis and neural invasion, and also with the poor prognosis of patients. Immunocytochemical analyses in pancreatic cancer cells demonstrated that CAP1 colocalized to the leading edge of lamellipodia with actin. Knockdown of CAP1 by RNA interference resulted in the reduction of lamellipodium formation, motility, and invasion of pancreatic cancer cells. This is the first report demonstrating the overexpression of CAP1 in pancreatic cancers and suggesting the involvement of CAP1 in the aggressive behavior of pancreatic cancer cells.

Original languageEnglish
Pages (from-to)425-432
Number of pages8
JournalLaboratory Investigation
Volume89
Issue number4
DOIs
Publication statusPublished - 2009 Apr

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Pancreatic Neoplasms
Adenylyl Cyclases
Cell Movement
Neoplasms
Proteins
Pseudopodia
Heterografts
SCID Mice
Neoplasm Genes
Gene Expression Profiling
RNA Interference
Actins
Early Diagnosis
Lymph Nodes
Neoplasm Metastasis
Gene Expression

Keywords

  • CAP1
  • Metastasis
  • Microarray
  • Pancreatic cancer
  • Prognosis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology
  • Molecular Biology

Cite this

Adenylate cyclase-associated protein 1 overexpressed in pancreatic cancers is involved in cancer cell motility. / Yamazaki, Ken; Takamura, Masaaki; Masugi, Yohei; Mori, Taisuke; Du, Wenlin; Hibi, Taizo; Hiraoka, Nobuyoshi; Ohta, Tsutomu; Ohki, Misao; Hirohashi, Setsuo; Sakamoto, Michiie.

In: Laboratory Investigation, Vol. 89, No. 4, 04.2009, p. 425-432.

Research output: Contribution to journalArticle

Yamazaki, K, Takamura, M, Masugi, Y, Mori, T, Du, W, Hibi, T, Hiraoka, N, Ohta, T, Ohki, M, Hirohashi, S & Sakamoto, M 2009, 'Adenylate cyclase-associated protein 1 overexpressed in pancreatic cancers is involved in cancer cell motility', Laboratory Investigation, vol. 89, no. 4, pp. 425-432. https://doi.org/10.1038/labinvest.2009.5
Yamazaki, Ken ; Takamura, Masaaki ; Masugi, Yohei ; Mori, Taisuke ; Du, Wenlin ; Hibi, Taizo ; Hiraoka, Nobuyoshi ; Ohta, Tsutomu ; Ohki, Misao ; Hirohashi, Setsuo ; Sakamoto, Michiie. / Adenylate cyclase-associated protein 1 overexpressed in pancreatic cancers is involved in cancer cell motility. In: Laboratory Investigation. 2009 ; Vol. 89, No. 4. pp. 425-432.
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