Direct association of TSLC1 and DAL-1, two distinct tumor suppressor proteins in lung cancer.
The tumor suppressor gene TSLC1, which we recently identified in human non-small cell lung cancer, encodes a membrane glycoprotein of the immunoglobulin superfamily. Here, we report that TSLC1 directly associates with DAL-1, a gene product of another lung tumor suppressor belonging to the protein 4.1 family. TSLC1 additionally interacts with the actin filament through DAL-1 at the cell-cell attached site where the complex formation of TSLC1 and DAL-1 is dependent on the integrity of actin cytoskeleton. Redistribution of both TSLC1 and DAL-1 to the newly generated membrane ruffling areas suggests that these proteins are also involved in cell motility accompanying the actin rearrangement. Furthermore, restoration of TSLC1 expression strongly suppressed the metastasis of a human non-small cell lung cancer cell line, A549, from the spleen to the liver in nude mice. These findings, together with frequent loss of their expression in lung cancers, suggest that TSLC1 and DAL-1 play a critical role in the same pathway involved in the suppression of lung tumor formation and metastasis.
Yageta
Mika
M
Tumor Suppression & Functional Genomics Project, National Cancer Center Research Institute, 5-1-1 Tsukuji, Chuo-ku, Tokyo 104-0045, Japan.
Kuramochi
Masami
M
Masuda
Mari
M
Fukami
Takeshi
T
Fukuhara
Hiroshi
H
Maruyama
Tomoko
T
Shibuya
Masabumi
M
Murakami
Yoshinori
Y
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007136:Immunoglobulins; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D000199:Actins; C403514:CADM1 protein, human; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; C116887:EPB41L3 protein, human; D007136:Immunoglobulins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; D015638:Cytochalasin D