Silencing of the ARP2/3 complex disturbs pancreatic cancer cell migration

Anticancer Res. 2013 Jan;33(1):45-52.

Abstract

Background: Actin-related protein 2/3 (ARP2/3) complex is an actin nucleator responsible for actin cytoskeleton branching which is essential for efficient cell migration.

Materials and methods: The expression of the seven ARP2/3 complex subunits was assessed in pancreatic cancer cell lines and in normal pancreatic samples by quantitative RT-PCR. siRNA-mediated silencing was used to study the contribution of each ARP2/3 complex member to pancreatic cancer cell migration.

Results: ARPC3 and ARPC4 were the most highly expressed complex members, while ARPC1B and ARPC2 were expressed at low levels. Silencing of the ARP2/3 complex subunits typically resulted in reduced cell migration capacity. In particular, silencing of ARPC4 significantly reduced cell migration in all studied cell lines, with a major impact on Hs700T and HPAFII migration (50% and 68% decrease, p<0.001).

Conclusion: We offer comprehensive expression data on the ARP2/3 complex members for pancreatic cancer and normal pancreas. In addition, we show cell line-specific differences in ARP2/3 complex subunit dependency on cell migratory potential, and suggest ARPC4 to be one of the key members of the ARP2/3 complex in pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton* / metabolism
  • Actin-Related Protein 2-3 Complex* / genetics
  • Actin-Related Protein 2-3 Complex* / metabolism
  • Actins / genetics*
  • Actins / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cytoskeletal Proteins* / genetics
  • Cytoskeletal Proteins* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / metabolism
  • Pancreatic Neoplasms* / pathology
  • RNA, Small Interfering

Substances

  • ARPC4 protein, human
  • Actin-Related Protein 2-3 Complex
  • Actins
  • Cytoskeletal Proteins
  • RNA, Small Interfering