Actinin-4, a novel actin-bundling protein associated with cell motility and cancer invasion

J Cell Biol. 1998 Mar 23;140(6):1383-93. doi: 10.1083/jcb.140.6.1383.

Abstract

Regulation of the actin cytoskeleton may play a crucial role in cell motility and cancer invasion. We have produced a monoclonal antibody (NCC- Lu-632, IgM, k) reactive with an antigenic protein that is upregulated upon enhanced cell movement. The cDNA for the antigen molecule was found to encode a novel isoform of nonmuscle alpha-actinin. This isoform (designated actinin-4) was concentrated in the cytoplasm where cells were sharply extended and in cells migrating and located at the edge of cell clusters, but was absent from focal adhesion plaques or adherens junctions, where the classic isoform (actinin-1) was concentrated. Actinin-4 shifted steadily from the cytoplasm to the nucleus upon inhibition of phosphatidylinositol 3 kinase or actin depolymerization. The cytoplasmic localization of actinin-4 was closely associated with an infiltrative histological phenotype and correlated significantly with a poorer prognosis in 61 cases of breast cancer. These findings suggest that cytoplasmic actinin-4 regulates the actin cytoskeleton and increases cellular motility and that its inactivation by transfer to the nucleus abolishes the metastatic potential of human cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinin*
  • Actins / metabolism
  • Amino Acid Sequence
  • Antibody Specificity
  • Breast Neoplasms
  • Cell Movement / physiology*
  • Cell Nucleus / chemistry
  • Cell Nucleus / metabolism
  • Cloning, Molecular
  • Colonic Neoplasms
  • DNA, Complementary
  • Female
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Keratinocytes / chemistry
  • Keratinocytes / cytology
  • Lung Neoplasms
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / immunology
  • Microfilament Proteins / metabolism*
  • Molecular Sequence Data
  • Neoplasm Invasiveness / physiopathology*
  • Predictive Value of Tests
  • Prognosis
  • RNA, Messenger / metabolism
  • Tumor Cells, Cultured / chemistry
  • Tumor Cells, Cultured / cytology
  • Urinary Bladder Neoplasms

Substances

  • ACTN4 protein, human
  • Actins
  • DNA, Complementary
  • Microfilament Proteins
  • RNA, Messenger
  • actin filament bundling proteins
  • Actinin

Associated data

  • GENBANK/D89980