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临床问题。已经揭示了细胞内囊泡的转运与各种适当的细胞器一起传递多种分子，参与了这些过程。积累的证据表明，细胞内囊泡的转运在空间和临时受到各种分子的调节，包括胞外囊肿，rab gtpase，snares等。我们最近已经确定α-催化蛋白是Snares的一种结合伴侣。在语法素成员中，α-催化蛋白优先结合Syntaxin-4，据报道，在母细胞的前缘富集。此外，已经表明，与正常组织相比，星形胶质细胞瘤的mRNAα-催化蛋白水平升高。因此，α-催化蛋白不仅通过其前缘的语法4的相互作用，而且在肿瘤发生中都参与细胞运动。然而，α-TA的作用…更多的xilin在肿瘤发生中仍然弹性。然后，在这项研究中，我们试图解决这个问题。在结肠中的各种肿瘤细胞中，几乎未检测到α-催化蛋白。另一方面，迄今为止检查的几乎所有恶性肿瘤中，几乎所有的恶性肿瘤都显着检测到α-纳米蛋白，这表明与正常组织中的α-催化蛋白的表达水平增加了。结果暗示了α-催化蛋白表达水平的增加与肿瘤发生之间的关系。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-催化蛋白相互作用分子。与新生多肽相关的复合物（αNAC）的α-亚x素相互作用，该复合物（αNAC）与c-Jun依赖性的α-纳米蛋白的转录过表达有关，抑制了αNAC从胞质溶液中转移到核的αNNN的α-TAXAXICAXICINCTIONACTION-α-TAXAXINNN与α-TAXAXIN的相互作用，这与α-TAXAXIN的相互作用有关。总之，我们目前的研究强烈暗示α-催化蛋白直接或间接参与了肿瘤发生。然而，进一步的研究对于我们了解α-催化蛋白在肿瘤发生中的作用方式是必不可少的。较少的

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