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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.
K Honda, and
T Yamada, and
R Endo, and
Y Ino, and
M Gotoh, and
H Tsuda, and
Y Yamada, and
H Chiba, and
S Hirohashi
September 2018,
The Journal of biological chemistry,
K Honda, and
T Yamada, and
R Endo, and
Y Ino, and
M Gotoh, and
H Tsuda, and
Y Yamada, and
H Chiba, and
S Hirohashi
October 2000,
British journal of cancer,
K Honda, and
T Yamada, and
R Endo, and
Y Ino, and
M Gotoh, and
H Tsuda, and
Y Yamada, and
H Chiba, and
S Hirohashi
January 2015,
Cancer letters,
K Honda, and
T Yamada, and
R Endo, and
Y Ino, and
M Gotoh, and
H Tsuda, and
Y Yamada, and
H Chiba, and
S Hirohashi
November 2020,
EMBO reports,
K Honda, and
T Yamada, and
R Endo, and
Y Ino, and
M Gotoh, and
H Tsuda, and
Y Yamada, and
H Chiba, and
S Hirohashi
October 2000,
Oncogene,
K Honda, and
T Yamada, and
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H Tsuda, and
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S Hirohashi
November 2013,
Immunological reviews,
K Honda, and
T Yamada, and
R Endo, and
Y Ino, and
M Gotoh, and
H Tsuda, and
Y Yamada, and
H Chiba, and
S Hirohashi
March 2011,
Oncology reports,
K Honda, and
T Yamada, and
R Endo, and
Y Ino, and
M Gotoh, and
H Tsuda, and
Y Yamada, and
H Chiba, and
S Hirohashi
February 2015,
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer,
K Honda, and
T Yamada, and
R Endo, and
Y Ino, and
M Gotoh, and
H Tsuda, and
Y Yamada, and
H Chiba, and
S Hirohashi
August 1999,
Proceedings of the National Academy of Sciences of the United States of America,
K Honda, and
T Yamada, and
R Endo, and
Y Ino, and
M Gotoh, and
H Tsuda, and
Y Yamada, and
H Chiba, and
S Hirohashi
June 2015,
Journal of periodontal research,
