Roles and mode of action of Taxilin family in invasion and metastasis of malignant cells

Taxilin家族在恶性肿瘤细胞侵袭转移中的作用及作用方式

基本信息

批准号：
17590276
负责人：
SHIRATAKI Hiromichi
金额：
$ 2.3万
依托单位：
Dokkyo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590276/
关键词：
Taxilin SNARE Syntaxin Intracellular vesicle transport Cancer Cell motility

项目摘要

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 … More 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

抑制恶性细胞的侵袭和转移是一个紧迫的问题。已经发现，细胞内囊泡运输通过将多种分子递送至各自适当的细胞器来参与这些过程。越来越多的证据表明，细胞内囊泡运输是空间和转移的。时间上受到多种分子的调节，包括外囊、Rab GTPases、SNARE 等。我们最近发现 α-taxilin 是突触蛋白的结合伴侣。在突触蛋白成员中，α-taxilin 优先与突触蛋白 4 结合，据报道，突触蛋白 4 富集于运动细胞的前缘。此外，α-taxilin 的 mRNA 水平在星形细胞瘤中增加。因此，α-taxilin 可能不仅通过其前缘突触蛋白 4 的相互作用参与细胞运动，而且还参与肿瘤发生。然而，α-taxilin 在肿瘤发生中的作用仍然难以捉摸，在本研究中，除了结肠中的神经内分泌细胞外，α-Taxilin 几乎没有被检测到。迄今为止，在几乎所有检查的恶性组织中均显着检测到α-taxilin，表明恶性组织中α-taxilin的表达水平比正常组织中的α-taxilin表达水平增加。该结果暗示α-taxilin的表达水平增加之间的关系。然后，为了阐明这种关系，我们尝试使用酵母双杂交方法分离 α-taxilin 相互作用分子，α-taxilin 与新生多肽相关复合物的 α 亚基相互作用。 αNAC)，通过从细胞质到细胞核的易位参与 c-Jun 依赖性转录过程。α-taxilin 的过度表达抑制了 αNAC 从细胞质的易位。细胞质到细胞核，表明 α-taxilin 通过与 αNAC 强烈相互作用参与转录过程，我们目前的研究表明 α-taxilin 直接或间接参与肿瘤发生。对α-taxilin在肿瘤发生中的作用方式了解较少。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

CRMP-2 is involved in kinesin-1-dependent transport of the Sra-1/WAVW1 complex and axon formation

CRMP-2 参与 Sra-1/WAVW1 复合物的驱动蛋白 1 依赖性运输和轴突形成

DOI：
发表时间：
2005
期刊：
Mol.Cell Biol. 25
影响因子：
0
作者：
Kawano;Y.;Yoshimura;T.;Tsuboi;D.;Kawabata;S.;Kaneko-Kawano;T.;Shirataki;H.;Takenawa;T.;Kaibuchi;K
通讯作者：
K

Interaction of the taxilin family with the nascent polypeptide-associated complex that is involved in the transcriptional and translational process

紫杉素家族与参与转录和翻译过程的新生多肽相关复合物的相互作用