Isolation of the TSLL1 and TSLL2 genes, members of the tumor suppressor TSLC1 gene family encoding transmembrane proteins

Fukuhara, Hiroshi; Kuramochi, Masami; Nobukuni, Takahiro; Fukami, Takeshi; Saino, Makoto; Maruyama, Tomoko; Nomura, Sachio; Sekiya, Takao; Murakami, Yoshinori

doi:10.1038/sj.onc.1204696

Cited by 63 publications

(65 citation statements)

References 15 publications

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“…On the other hand, the cytoplasmic domain of TSLC1 is relatively short of 46 amino acids but contains a couple of important motifs, a protein 4.1-binding motif just adjacent to the transmembrane domain and a PDZ-binding motif (class II) at the carboxyterminal end (Songyang et al, 1997;Fukuhara et al, 2001;Fukami et al, 2002). We have recently demonstrated that the 4.1-binding motif is essential for the association of TSLC1 with DAL-1/4.1B, another tumor suppressor protein in lung cancer .…”

Section: Introductionmentioning

confidence: 99%

Association of a lung tumor suppressor TSLC1 with MPP3, a human homologue of Drosophila tumor suppressor Dlg

Fukuhara¹,

Masvuda²,

Sakurai-Yageta³

et al. 2003

Oncogene

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We have previously identified the tumor suppressor in lung cancer 1 (TSLC1) gene as a novel tumor suppressor in human non-small cell lung cancer (NSCLC) by functional complementation. TSLC1 encodes a membrane glycoprotein belonging to an immunoglobulin superfamily and participates in cell adhesion. A truncating mutation of the TSLC1 corresponding to its cytoplasmic domain in a primary NSCLC tumor suggests that this domain is important for tumor suppressor activity. Here, we report that TSLC1 directly associates with MPP3, one of the human homologues of a Drosophila tumor suppressor gene, Discs large (Dlg). This interaction was dependent on the presence of a PDZ-binding motif at the carboxyl terminus of TSLC1. Furthermore, TSLC1 and MPP3 were colocalized at the cell-cell attachment sites in both a low and a high cell density. The MPP3 gene was expressed in normal lung as well as in many tissues examined except for peripheral blood lymphocytes but lost its expression in one of the nine NSCLC cell lines. These results suggest that TSLC1 and MPP3 are involved in the same cascade of cell-cell interaction, and that the disruption of this cascade might lead cells to malignant growth and tumor formation in lung cancer.

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Section: Introductionmentioning

confidence: 99%

Association of a lung tumor suppressor TSLC1 with MPP3, a human homologue of Drosophila tumor suppressor Dlg

Fukuhara¹,

Masvuda²,

Sakurai-Yageta³

et al. 2003

Oncogene

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“…These include the nectin-like (Necl) cell adhesion molecules, a family of immunoglobulin (Ig)-like CAMs also called the cell adhesion molecules (Cadm), the TSLC1-like proteins (Fukuhara et al, 2001) and the synaptic cell adhesion molecules (SynCAMs) (Biederer et al, 2002). Necl-1 and Necl-2 are expressed along the axon internode and are directly apposed by Necl-4, and potentially Necl-2, on the inner turn, that is, the periaxonal Schwann cell membrane (Maurel et al, 2007;Spiegel et al, 2007).…”

Section: The Internodementioning

confidence: 99%

Molecular domains of myelinated axons in the peripheral nervous system

Salzer

Brophy

Peles

2008

Glia

200

172

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Myelinated axons are organized into a series of specialized domains with distinct molecular compositions and functions. These domains, which include the node of Ranvier, the flanking paranodal junctions, the juxtaparanodes, and the internode, form as the result of interactions with myelinating Schwann cells. This domain organization is essential for action potential propagation by saltatory conduction and for the overall function and integrity of the axon. V

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“…TSLC1 encodes a 75 kDa N-linked glycoprotein that mediates intracellular adhesion through homophilic interactions in a Ca 2 þ /Mg 2 þ independent manner . This 75 kDa N-linked glycoprotein comprises three Ig-like C2-type domains, a single hydrophobic membranespanning a-helix and a short cytoplasmic domain of 46 amino acids that contains a protein 4.1-binding motif just adjacent to the transmembrane domain and a PDZbinding motif (class II) at the carboxy-terminal end (Songyang et al, 1997;Fukuhara et al, 2001). The 4.1 binding motif at the juxtamembrane region is essential for the interaction with the tumor suppressor protein in lung cancer, DAL-1 (differentially expressed in adenocarcinoma of the lung-1, EPB41L3), which is localized at the cytoplasmic side of the cell membrane (Tran et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Expression and methylation pattern of TSLC1 cascade genes in lung carcinomas

et al. 2005

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TSLC1 (tumor suppressor in lung cancer-1, IGSF4) encodes a member of the immunoglobulin superfamily molecules, which is involved in cell-cell adhesion. TSLC1 is connected to the actin cytoskeleton by DAL-1 (differentially expressed in adenocarcinoma of the lung-1, EPB41L3) and it directly associates with MPP3, one of the human homologues of a Drosophila tumor suppressor gene, Discs large. Recent data suggest that aberrant promoter methylation is important for TSLC1 inactivation in lung carcinomas. However, little is known about the other two genes in this cascade, DAL-1 and MPP3. Thus, we investigated the expression and methylation patterns of these genes in lung cancer cell lines, primary lung carcinomas and nonmalignant lung tissue samples. By reverse transcription-polymerase chain reaction, loss of TSLC1 expression was observed in seven of 16 (44%) non-small-cell lung cancer (NSCLC) cell lines and in one of 11 (9%) small-cell lung cancer (SCLC) cell lines, while loss of DAL-1 expression was seen in 14 of 16 (87%) NSCLC cell lines and in four of 11 (36%) SCLC cell lines. By contrast, MPP3 expression was found in all tumor cell lines analysed. Similar results were obtained by microarray analysis. TSLC1 methylation was seen in 13 of 39 (33%) NSCLC cell lines, in one of 11 (9%) SCLC cell lines and in 100 of 268 (37%) primary NSCLCs. DAL-1 methylation was observed in 17 of 39 (44%) NSCLC cell lines, in three of 11 (27%) SCLC cell lines and in 147 of 268 (55%) primary NSCLCs. In tumors of NSCLC patients with stage II-III disease, DAL-1 methylation was seen at a statistically significant higher frequency compared to tumors of patients with stage I disease. A significant correlation between loss of expression and methylation of the genes in lung cancer cell lines was found. Overall, 65% of primary NSCLCs had either TSLC1 or DAL-1 methylated. Methylation of one of these genes was detected in 59% of NSCLC cell lines; however, in SCLC cell lines, methylation was much less frequently observed. The majority of nonmalignant lung tissue samples was not TSLC1 or DAL-1 methylated. Re-expression of TSLC1 and DAL-1 was seen after treatment of lung cancer cell lines with 5-aza-2 0 -deoxycytidine. Our results suggest that methylation of TSLC1 and/or DAL-1, leading to loss of their expression, is an important event in the pathogenesis of NSCLC. Oncogene (2006) 25, 959-968.

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Isolation of the TSLL1 and TSLL2 genes, members of the tumor suppressor TSLC1 gene family encoding transmembrane proteins

Cited by 63 publications

References 15 publications

Association of a lung tumor suppressor TSLC1 with MPP3, a human homologue of Drosophila tumor suppressor Dlg

Association of a lung tumor suppressor TSLC1 with MPP3, a human homologue of Drosophila tumor suppressor Dlg

Molecular domains of myelinated axons in the peripheral nervous system

Expression and methylation pattern of TSLC1 cascade genes in lung carcinomas

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