RRC ID 39135
Author Honda K, Yamada T, Endo R, Ino Y, Gotoh M, Tsuda H, Yamada Y, Chiba H, Hirohashi S.
Title Actinin-4, a novel actin-bundling protein associated with cell motility and cancer invasion.
Journal J Cell Biol
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.
Volume 140(6)
Pages 1383-93
Published 1998-3-23
DOI 10.1083/jcb.140.6.1383
PMID 9508771
PMC PMC2132673
MeSH 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
IF 8.811
Times Cited 338
Human and Animal Cells IMC-2(RCB0276) MRC-5