Myosin X调控外泌体信号参与结直肠癌侵袭、转移的分子机制

结直肠癌(CRC)远处转移是导致患者死亡和治疗失败的主要原因。研究CRC转移机制，发现调控CRC转移的关键靶分子，对预防和治疗结直肠癌转移有重要意义。. 我们在前期的研究中发现，Myosin X，一个位于丝状伪足尖端的非传统型肌球蛋白，通过促进丝状伪足生长、调节磷酸化粘着斑激酶表达等机制参与分泌型RGMc诱导的CRC肝转移。活细胞成像、免疫沉淀研究进一步发现，外泌体，一种由细胞分泌的囊泡状结构可能通过调控肿瘤微环境参与了Myosin X介导的CRC侵袭与转移。. 本项目在前期研究的基础上，通过凝胶层析、差异蛋白组学等深入探讨Myosin X对外泌体的调控作用。利用已成功建立的稳定细胞系和CRC肝转移模型，体内、外验证Myosin X调控的外泌体信号在结直肠癌侵袭、转移中的关键作用，并探索分子机制。这将为有效预防和治疗结直肠癌肝转移提供新的思维方向和理论依据。

Distant metastasis is responsible to the death and treatment failure in patients with CRC. Exploring the mechanisms underlying CRC metastasis and finding the key target molecules has great implications for the the prevention and treatment of colorectal cancer metastasis.. In our previous study, we found Myosin X, an unconventional myosin locating at the tip of filopodia, played an important role in sRGMc-mediated liver metastasis of CRC by promoting the growth of filopodia and regulating the phosphorylated focal adhesion kinase (FAK). Live image and immuno-precipitaion assay suggest exsomes, a kind of membrane vesicles secreted by tumor cell, regulated tumor microenviro- ment and promoted CRC metastasis. Myosin X may functions in the trafficking pathway of exsomes.. Based on our previous study, the role of Myosin X in the trafficking of exsomes will be explored further by gel chromatography, two-dimensional difference gel electr ophoresis, and other techniques. Established stable cell line knocked down Myosin X and an animal model with liver metastasis of CRC will be used to detect the role and molecular mechanisms underlying exosome signaling regulated by Myosin X in the invasion and metastasis of colorectal cancer. The findings of this project will enrich the theory of malignant tumor metastasis and provide a novel way for the the prevention and treatment of colorectal cancer metastasis..