2004 Fiscal Year Final Research Report Summary
Analysis of cell adhesion and polarity formation by a novel tumor suppressor protein TSLC1 and its related molecules
| Project/Area Number |
15590262
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | National Cancer Center Research Institute |
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Principal Investigator |
MURAKAMI Yoshinori National Cancer Center Research Institute, Tumor Suppression & Functional Genomics Project, Project Leader, がん抑制ゲノム研究プロジェクト, プロジェクトリーダー (30182108)
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| Project Period (FY) |
2003 – 2004
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| Keywords | TSLC1 / Proteins 4.1 / Membrane assopciated guanylate kinase / Cel adhesion / Epithelial like cell structure / RNAi |
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| Research Abstract |
Morphological transformation is a fundamental feature of malignant cancer cells. The tumor suppressor, TSLC1/IGSF4, is involved in cell adhesion and preferentially inactivated in invasive cancer. We have previously shown that TSLC1 associates with an actin-binding protein, DAL-1/4.1B, and a scaffold protein, membrane protein palmitoylated 3(MPP3). Here, we identified MPP1/p55 and MPP2/DLG2 as additional cytoplasmic proteins binding to TSLC1 and investigated the roles of the TSLC1 cascade in epithelial cell morphology and its malignant transformation. MPP1, MPP2, and MPP3 interacted directly with DAL-1, forming a tripartite complex with TSLC1. Whereas these complexes localized along the cell membranes in confluent HEK293 cells, only MPP2, but not MPP1 or MPP3, was recruited to the TSLC1-DAL-1 complex in the early process of cell adhesion. When the TSLC1 function was abrogated by RNAi, HEK293 losed epithelial-like structure and showed flat morphology with immature cell adhesion. Furthermore, DAL-1 and MPP2, as well as E-cadherin and ZO-1, were mislocalized from the membrane. Loss of TSLC1 was also correlated with the transformed phenotype of lung cancer cells. These findings suggest that TSLC1 is involved in the formation of epithelial-like cell structure with DAL-1 and MPPs, while loss of its function could cause morphological transformation of cancer cells.
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Research Products
(12 results)
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[Journal Article] Promoter methylation of the DAL-1/4.1B predicts poor prognosis in non-small cell lung cancer.2005
Author(s)
Kikuchi, S., Yamada, D., Fukami, T., Masuda, M., Sakurai-Yageta, M., Williams, Y.N., Maruyama, T., Asamura, H., Matsuno, Y., Onizuka, M., Murakami, Y.
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Journal Title
Clin.Cancer Res. 11
Pages: 2954-2961
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Overexpression of a cell adhesion molecule, TSLC1,as a possible molecular marker for acute type of adult T-cell leukemia.2005
Author(s)
Sasaki, H., Nishikata, I., Shiraga, T., Akamatsu, E., Ishida, Y., Fukami, T., Hidaka, T., Kubuki, Y., Okayama, A., Hamada, K., Okabe, H., Murakami.Y., Tsubouchi, H., Morishita, K.
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Journal Title
Blood 105
Pages: 1204-1213
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Inhibition of angiogenesis in human glioma cell lines by antisense RNA from the soluble guanylate cyclase genes, GUCY1A3 and GUCY1B3.2004
Author(s)
Saino, M., Maruyama, T., Sekiya, T., Kayama, T., Murakami, Y.
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Journal Title
Oncol.Rep. 12
Pages: 47-52
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Association of a lung tumor suppressor TSLC1 with MPP3,a human homologue of droso phila tumor suppressor Dig.2003
Author(s)
Fukuhara, H., Masuda, M., Yageta, M., Fukami, T., Kuramochi, M., Maruyama, T., Kitamura, T., Murakami, Y.
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Journal Title
Oncogene 22
Pages: 6160-6165
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Promoter methylation of the TSLC1 gene in advanced lung tumors and various cancer cell lines.2003
Author(s)
Fukami, F., Fukuhara, H., Kuramochi, M., Maruyama, T., Isogai, K., Sakamoto, M., Takamoto, S., Murakami, Y.
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Journal Title
Int J Cancer 107
Pages: 53-59
Description
「研究成果報告書概要(欧文)」より
