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

• 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

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临床亟待解决的问题。研究表明，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，细胞内囊泡运输在空间和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（SNARE 的一个组成部分）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，已经表明，与正常组织相比，星形细胞瘤中α-taxilin的mRNA水平增加。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-ta xilin 在肿瘤发生中的作用仍然难以捉摸。然后，在本研究中我们试图解决这个问题。除结肠中的神经内分泌细胞外，在各种组织中几乎检测不到α-Taxilin。另一方面，在迄今为止检查的几乎所有恶性组织中均显着检测到α-taxilin，表明恶性组织中α-taxilin的表达水平与正常组织中的表达水平相比增加。该结果暗示α-taxilin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-taxilin 相互作用分子。 α-Taxilin 与新生多肽相关复合物 (αNAC) 的 α 亚基相互作用，该复合物通过从细胞质易位到细胞核参与 c-Jun 依赖性转录过程。 α-taxilin 的过度表达抑制 αNAC 从细胞质到细胞核的易位，表明 α-taxilin 通过与 αNAC 相互作用参与转录过程。总之，我们目前的研究强烈表明 α-taxilin 直接或间接参与肿瘤发生。然而，为了了解α-taxilin在肿瘤发生中的作用模式，还需要进一步的研究。较少的

项目成果

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

• 发表时间: 2005
• 期刊: Mol.Cell Biol. 25
• 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

• 发表时间: 2005
• 期刊: Genes to Cells 10
• 作者: Yoshida;K.;Nogami;S.;Satoh;S.;Tanaka-Nakadate S.;Hiraishi;H.;Terano;A.;Shirataki;H.
• 通讯作者: H.