2006 Fiscal Year Final Research Report Summary
Roles and mode of action of Taxilin family in invasion and metastasis of malignant cells
| Project/Area Number |
17590276
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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 |
Pathological medical chemistry
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| Research Institution | Dokkyo Medical University |
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Principal Investigator |
SHIRATAKI Hiromichi Dokkyo Medical University, Graduate school of Medicine, Department of Molecular and Cell Biology, Professor, 医学部, 教授 (90249962)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Taxilin / SNARE / Syntaxin / Intracellular vesicle transport / Cancer / Cell motility |
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| Research Abstract |
It is an urgent clinical issue to inhibit invasion and metastasis of malignant cells. It has been revealed that intracellular vesicle transport is involved in these processes through delivering a wide variety of molecules to the respective proper organelles. Accumulating evidence indicates that intracellular vesicle transport is spatially and temporally regulated by a wide variety of molecules including exocyst, Rab GTPases, SNAREs, and so on. We have recently identified α-taxilin as a binding partner of syntaxin, a component of SNAREs. Among syntaxin members, α-taxilin preferentially binds to syntaxin-4, which has been reported to enrich at the leading edge of motile cells. Moreover, it has been revealed that mRNA level of α-taxilin is increased in astrocytoma compared with that in normal tissues. Therefore, it is possible that α-taxilin is involved not only in cell motility through its interaction of syntaxin-4 at the leading edge but also in the tumorigenesis. However, roles of α-ta
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xilin in the tumorigenesis remain elusive. Then, in this study we attempted to address this. α-Taxilin was hardly detected in various tissues except for neuroendocrine cells in the colon. On the other hand, α-taxilin was significantly detected in almost all of the malignant tissues examined so far, indicating that expression levels of α-taxilin in the malignant tissues are increased compared with those in normal tissues. The result implies a relationship between increase in expression level of α-taxilin and the tumorigenesis. Then, to clarify this relationship, we attempted to isolate α-taxilin-interacting molecules using the yeast two-hybrid method. α-Taxilin was interacted with the alpha-subunit of the nascent polypeptide-associated complex (αNAC), which is involved in a c-Jun-dependent transcriptional process through translocation from the cytosol to the nucleus. Over-expression of α-taxilin inhibited the translocation of αNAC from the cytosol to the nucleus, suggesting that α-taxilin is involved in the transcriptional process through its interaction with αNAC. Together, our present studies strongly imply that α-taxilin is directly or indirectly involved in the tumorigenesis. However, further study is necessary for our understanding of mode of action of α-taxilin in the tumorigenesis. Less
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[Journal Article] Interaction of the taxilin family with the nascent polypeptide-associated complex that is involved in the transcriptional and translational process2005
Author(s)
Yoshida, K., Nogami, S., Satoh, S., Tanaka-Nakadate S., Hiraishi, H., Terano, A., Shirataki, H.
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Journal Title
Genes to Cells 10
Pages: 465-476
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] CRMP-2 is involved in kinesin-1-dependent transport of the Sra-1/WAVW1 complex and axon formation2005
Author(s)
Kawano, Y., Yoshimura, T., Tsuboi, D., Kawabata, S., Kaneko-Kawano, T., Shirataki, H., Takenawa, T., Kaibuchi, K
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Journal Title
Mol.Cell Biol. 25
Pages: 9920-9935
Description
「研究成果報告書概要(欧文)」より
