Upregulated expression of CAP1 is associated with tumor migration and metastasis in hepatocellular carcinoma

Pathol Res Pract. 2014 Mar;210(3):169-75. doi: 10.1016/j.prp.2013.11.011. Epub 2013 Dec 5.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers that exhibits high incidences of intrahepatic metastasis and tumor recurrence. Adenylate cyclase-associated protein 1 (CAP1), a protein involved in the regulation of actin filaments, was recently reported to play a role in cell motility and the pathology of pancreatic cancer. In this study, we examined a potential role of CAP1 in HCC progression, and found that CAP1 was overexpressed in HCC specimens compared with adjacent noncancerous liver tissues by Western blot analysis and real-time PCR assay. Further, immunohistochemical analysis in 107 HCC specimens revealed that overexpression of CAP1 was closely correlated only with tumor metastasis, but not with other clinicopathologic parameters. Univariate and multivariate survival analyses showed that CAP1 could be an independent prognostic factor for patients' survival. In addition, immunofluorescent assay demonstrated that CAP1 was colocalized with actin in the leading edge of lamellipodium in HCC cells. Importantly, knocking-down the expression of CAP1 using small interfering RNA (siRNA) targeting CAP1 led to impaired migration of HCC cells. Collectively, our results indicated that upregulated expression of CAP1 might contribute heavily to the metastasis of HCC.

Keywords: Adenylate cyclase-associated protein 1 (CAP1); Hepatocellular carcinoma; Migration; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / secondary
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Movement*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Female
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • RNA Interference
  • Survival Analysis
  • Time Factors
  • Transfection
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • CAP1 protein, human
  • Cell Cycle Proteins
  • Cytoskeletal Proteins