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 α-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.
Skip Nav Destination
Article navigation
23 March 1998
Article|
March 23 1998
Actinin-4, a Novel Actin-bundling Protein Associated with Cell Motility and Cancer Invasion
Kazufumi Honda,
Kazufumi Honda
*Pathology Division, National Cancer Center Research Institute, Tokyo 104, Japan; ‡Department of Oral and Maxillofacial Surgery, Tokyo Medical College, Tokyo 160, Japan; and §Hirohashi Cell Configuration Project, ERATO, Japan Scientific and Technology Corporation (JST), Tsukuba 300-26, Japan
Search for other works by this author on:
Tesshi Yamada,
Tesshi Yamada
*Pathology Division, National Cancer Center Research Institute, Tokyo 104, Japan; ‡Department of Oral and Maxillofacial Surgery, Tokyo Medical College, Tokyo 160, Japan; and §Hirohashi Cell Configuration Project, ERATO, Japan Scientific and Technology Corporation (JST), Tsukuba 300-26, Japan
Search for other works by this author on:
Ritsuko Endo,
Ritsuko Endo
*Pathology Division, National Cancer Center Research Institute, Tokyo 104, Japan; ‡Department of Oral and Maxillofacial Surgery, Tokyo Medical College, Tokyo 160, Japan; and §Hirohashi Cell Configuration Project, ERATO, Japan Scientific and Technology Corporation (JST), Tsukuba 300-26, Japan
Search for other works by this author on:
Yoshinori Ino,
Yoshinori Ino
*Pathology Division, National Cancer Center Research Institute, Tokyo 104, Japan; ‡Department of Oral and Maxillofacial Surgery, Tokyo Medical College, Tokyo 160, Japan; and §Hirohashi Cell Configuration Project, ERATO, Japan Scientific and Technology Corporation (JST), Tsukuba 300-26, Japan
Search for other works by this author on:
Masahiro Gotoh,
Masahiro Gotoh
*Pathology Division, National Cancer Center Research Institute, Tokyo 104, Japan; ‡Department of Oral and Maxillofacial Surgery, Tokyo Medical College, Tokyo 160, Japan; and §Hirohashi Cell Configuration Project, ERATO, Japan Scientific and Technology Corporation (JST), Tsukuba 300-26, Japan
Search for other works by this author on:
Hitoshi Tsuda,
Hitoshi Tsuda
*Pathology Division, National Cancer Center Research Institute, Tokyo 104, Japan; ‡Department of Oral and Maxillofacial Surgery, Tokyo Medical College, Tokyo 160, Japan; and §Hirohashi Cell Configuration Project, ERATO, Japan Scientific and Technology Corporation (JST), Tsukuba 300-26, Japan
Search for other works by this author on:
Yozo Yamada,
Yozo Yamada
*Pathology Division, National Cancer Center Research Institute, Tokyo 104, Japan; ‡Department of Oral and Maxillofacial Surgery, Tokyo Medical College, Tokyo 160, Japan; and §Hirohashi Cell Configuration Project, ERATO, Japan Scientific and Technology Corporation (JST), Tsukuba 300-26, Japan
Search for other works by this author on:
Hiroshige Chiba,
Hiroshige Chiba
*Pathology Division, National Cancer Center Research Institute, Tokyo 104, Japan; ‡Department of Oral and Maxillofacial Surgery, Tokyo Medical College, Tokyo 160, Japan; and §Hirohashi Cell Configuration Project, ERATO, Japan Scientific and Technology Corporation (JST), Tsukuba 300-26, Japan
Search for other works by this author on:
Setsuo Hirohashi
Setsuo Hirohashi
*Pathology Division, National Cancer Center Research Institute, Tokyo 104, Japan; ‡Department of Oral and Maxillofacial Surgery, Tokyo Medical College, Tokyo 160, Japan; and §Hirohashi Cell Configuration Project, ERATO, Japan Scientific and Technology Corporation (JST), Tsukuba 300-26, Japan
Search for other works by this author on:
Kazufumi Honda
*Pathology Division, National Cancer Center Research Institute, Tokyo 104, Japan; ‡Department of Oral and Maxillofacial Surgery, Tokyo Medical College, Tokyo 160, Japan; and §Hirohashi Cell Configuration Project, ERATO, Japan Scientific and Technology Corporation (JST), Tsukuba 300-26, Japan
Tesshi Yamada
*Pathology Division, National Cancer Center Research Institute, Tokyo 104, Japan; ‡Department of Oral and Maxillofacial Surgery, Tokyo Medical College, Tokyo 160, Japan; and §Hirohashi Cell Configuration Project, ERATO, Japan Scientific and Technology Corporation (JST), Tsukuba 300-26, Japan
Ritsuko Endo
*Pathology Division, National Cancer Center Research Institute, Tokyo 104, Japan; ‡Department of Oral and Maxillofacial Surgery, Tokyo Medical College, Tokyo 160, Japan; and §Hirohashi Cell Configuration Project, ERATO, Japan Scientific and Technology Corporation (JST), Tsukuba 300-26, Japan
Yoshinori Ino
*Pathology Division, National Cancer Center Research Institute, Tokyo 104, Japan; ‡Department of Oral and Maxillofacial Surgery, Tokyo Medical College, Tokyo 160, Japan; and §Hirohashi Cell Configuration Project, ERATO, Japan Scientific and Technology Corporation (JST), Tsukuba 300-26, Japan
Masahiro Gotoh
*Pathology Division, National Cancer Center Research Institute, Tokyo 104, Japan; ‡Department of Oral and Maxillofacial Surgery, Tokyo Medical College, Tokyo 160, Japan; and §Hirohashi Cell Configuration Project, ERATO, Japan Scientific and Technology Corporation (JST), Tsukuba 300-26, Japan
Hitoshi Tsuda
*Pathology Division, National Cancer Center Research Institute, Tokyo 104, Japan; ‡Department of Oral and Maxillofacial Surgery, Tokyo Medical College, Tokyo 160, Japan; and §Hirohashi Cell Configuration Project, ERATO, Japan Scientific and Technology Corporation (JST), Tsukuba 300-26, Japan
Yozo Yamada
*Pathology Division, National Cancer Center Research Institute, Tokyo 104, Japan; ‡Department of Oral and Maxillofacial Surgery, Tokyo Medical College, Tokyo 160, Japan; and §Hirohashi Cell Configuration Project, ERATO, Japan Scientific and Technology Corporation (JST), Tsukuba 300-26, Japan
Hiroshige Chiba
*Pathology Division, National Cancer Center Research Institute, Tokyo 104, Japan; ‡Department of Oral and Maxillofacial Surgery, Tokyo Medical College, Tokyo 160, Japan; and §Hirohashi Cell Configuration Project, ERATO, Japan Scientific and Technology Corporation (JST), Tsukuba 300-26, Japan
Setsuo Hirohashi
*Pathology Division, National Cancer Center Research Institute, Tokyo 104, Japan; ‡Department of Oral and Maxillofacial Surgery, Tokyo Medical College, Tokyo 160, Japan; and §Hirohashi Cell Configuration Project, ERATO, Japan Scientific and Technology Corporation (JST), Tsukuba 300-26, Japan
K. Honda is a recipient of a Research Resident Fellowship from the Foundation for Promotion of Cancer Research. This research was supported in part by a Grant-in-Aid for the Second Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health and Welfare, Japan.
The nucleotide sequence data reported in this paper will appear in the GenBank/EMBL/DDBJ nucleotide sequence databases under accession number D89980.
Address all correspondence to Setsuo Hirohashi, Pathology Division, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104, Japan. Tel.: +81-3-3542-2511, ext. 4102. Fax: +81-3-3248-2737. E-mail: [email protected]
Received:
July 21 1997
Revision Received:
January 13 1998
Online ISSN: 1540-8140
Print ISSN: 0021-9525
1998
J Cell Biol (1998) 140 (6): 1383–1393.
Article history
Received:
July 21 1997
Revision Received:
January 13 1998
Connected Content
This article has been corrected
Correction
Citation
Kazufumi Honda, Tesshi Yamada, Ritsuko Endo, Yoshinori Ino, Masahiro Gotoh, Hitoshi Tsuda, Yozo Yamada, Hiroshige Chiba, Setsuo Hirohashi; Actinin-4, a Novel Actin-bundling Protein Associated with Cell Motility and Cancer Invasion . J Cell Biol 23 March 1998; 140 (6): 1383–1393. doi: https://doi.org/10.1083/jcb.140.6.1383
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Connected Content
Advertisement
Advertisement
