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

抑制恶性肿瘤细胞的侵袭和转移是临床迫切需要解决的问题。研究表明，细胞内囊泡运输参与了这些过程，通过将各种各样的分子传递到各自的适当细胞器。越来越多的证据表明，胞内囊泡运输在空间和时间上受到多种分子的调节，包括胞囊、Rab GTPases、SNAREs等。我们最近发现α-taxilin是syntaxin的结合伙伴，syntaxin是SNAREs的一个组成部分。在syntaxin成员中，α-taxilin优先与syntaxin-4结合，据报道，syntaxin-4在运动细胞的前沿富集。此外，与正常组织相比，星形细胞瘤中α-taxilin mRNA水平升高。因此，α-taxilin不仅可能通过与前沿syntaxin-4的相互作用参与细胞运动，还可能参与肿瘤的发生。然而，α-ta…在肿瘤发生中的作用尚不清楚。在这项研究中，我们试图解决这个问题。除结肠神经内分泌细胞外，其余组织中均未检出α-Taxilin。另一方面，到目前为止，α-taxilin在几乎所有的恶性组织中均被检测到，表明α-taxilin在恶性组织中的表达水平较正常组织升高。结果提示α-taxilin表达水平升高与肿瘤发生有关。然后，为了明确这种关系，我们尝试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，α- nac参与了一个依赖c- jun的转录过程，通过从细胞质转移到细胞核。过表达α-taxilin抑制了αNAC从细胞质向细胞核的易位，提示α-taxilin通过与αNAC的相互作用参与了转录过程。总之，我们目前的研究强烈暗示α-taxilin直接或间接参与了肿瘤的发生。但α-taxilin在肿瘤发生中的作用机制还有待进一步研究。少

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