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
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DOI：
10.1038/sj.onc.1206744
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发表时间：
2003-09-18
期刊：
影响因子：
8
通讯作者：
Murakami, Y
中科院分区：
文献类型：
--
作者：
Fukuhara, H;Masvuda, M;Murakami, Y
我们之前通过功能互补将肺癌抑癌基因1（TSLC1）基因鉴定为人类非小细胞肺癌（NSCLC）的新型抑癌基因。 TSLC1 编码属于免疫球蛋白超家族的膜糖蛋白并参与细胞粘附。原发性 NSCLC 肿瘤中与其胞质结构域相对应的 TSLC1 截短突变表明该结构域对于肿瘤抑制活性很重要。在这里，我们报告 TSLC1 与 MPP3 直接相关，MPP3 是果蝇肿瘤抑制基因 Discs Large (Dlg) 的人类同源物之一。这种相互作用取决于 TSLC1 羧基末端是否存在 PDZ 结合基序。此外，在低细胞密度和高细胞密度下，TSLC1 和 MPP3 共定位于细胞-细胞附着位点。 MPP3 基因在正常肺以及除外周血淋巴细胞外的许多检查组织中表达，但在九种 NSCLC 细胞系之一中失去表达。这些结果表明，TSLC1和MPP3参与细胞-细胞相互作用的相同级联，并且该级联的破坏可能导致肺癌中细胞恶性生长和肿瘤形成。
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.