肌动蛋白家族成员Transgelin（TAGLN）的异常表达常与肿瘤转移相关而机制尚不明确。我们前期研究发现，结直肠癌（CRC）中TAGLN过表达、与上皮间质转化（EMT）相关、可促进肿瘤转移；且可能与转录因子HMGA2结合而导致细胞核转位。本项目拟针对CRC细胞、小鼠肿瘤转移模型及临床标本等，通过免疫印迹、侵袭和迁移实验、免疫沉淀、免疫荧光及双染色、凝胶移动迁徙率分析等方法，配合信号通路抑制剂和激动剂的使用，观测调控TAGLN的上游关键通路，明确TAGLN是否介导Akt、JNK和Wnt通路改变引起的结直肠癌EMT与转移；寻找TAGLN与HMGA2结合的确凿依据；并深入分析HMGA2对TAGLN介导的CRC侵袭和转移所发挥的调控作用。本研究将首次对TAGLN促进CRC转移的分子机制进行深入研究，拓展了对细胞骨架结合蛋白参与肿瘤转移分子机制的认识，也为CRC转移评估和治疗提供新的靶点。

The mechanisms that the abnormal expression of Transgelin (TAGLN) ,a member of actin-binding proteins, correlates with tumor metastasis were uncertain. Our previous study found that overexpressed TAGLN in colorectal cancer cell (CRC) induced epithelial-mesenchymal transition (EMT) and promoted colorectal metastasis. Among dozens of genes affected by TAGLN, transcription factor HMGA2 was noted and thought to induce the nuclear translocation of TAGLN. In present research, the cell lines, animal models of metastasis and clinical specimens of CRC would be employed and variety of experiments (western blot, cell migration and invasiveness assay, immunoprecipitation, immunofluorescence, et al) would be used, combined with pathways agonists and inhibitors, in order to illucidate the key pathways inducted the EMT and metastasis of CRC by TAGLN. Furthermore, the interaction between TAGLN and HMGA2 would be defined and the functions of TAGLN-binding- HMGA2 on the migration and invasiveness of CRC be extensively analyzed. This study will reveal for the first time the concrete mechanisms that TAGLN promotes CRC metastasis in vitro and in vivo and improve the comprehension of the molecular mechanisms that actin-binding proteins involve in the progress of metastasis, which would also provide novel targets for evaluation and therapies of CRC metastasis.