RRC ID |
39135
|
著者 |
Honda K, Yamada T, Endo R, Ino Y, Gotoh M, Tsuda H, Yamada Y, Chiba H, Hirohashi S.
|
タイトル |
Actinin-4, a novel actin-bundling protein associated with cell motility and cancer invasion.
|
ジャーナル |
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.
|
巻・号 |
140(6)
|
ページ |
1383-93
|
公開日 |
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
|
引用数 |
338
|
WOS 分野
|
CELL BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
IMC-2(RCB0276)
MRC-5 |