肌球蛋白1b调控外泌体分泌促进黑色素瘤转移的分子机制研究

黑色素瘤是一种由黑色素细胞过度增殖引发的恶性肿瘤，发病率逐年上升，因其极强的侵袭性、转移性，成为临床治疗的最大障碍。外泌体作为信息载体，可参与细胞间以及细胞与微环境间的信息交流，近年来，其在肿瘤侵袭转移方面的重要作用受到了广泛关注。肌球蛋白1b是一种广泛存在的动力蛋白，研究发现其在人类多种恶性肿瘤中异常表达，且与部分肿瘤发展及不良预后有关。前期实验发现肌球蛋白1b与黑色素瘤转移具有相关性，并可以影响外泌体的产生，但是具体调节机制并不清楚。据此，我们以外泌体为切入点，提出“肌球蛋白1b调控外泌体分泌促进黑色素瘤转移”这一假说，并通过分析多泡体转运，构建肌球蛋白1b突变体和筛选其相互作用蛋白，以及小鼠黑色素瘤肺转移模型，深入探索肌球蛋白1b促进外泌体分泌和黑色素瘤转移的分子机制，旨在为黑色素瘤综合治疗提供新的分子治疗靶点及理论依据。

Melanoma is a malignant tumor caused by excessive proliferation of melanocytes, and its incidence and mortality continue to increase in the world. Widespread metastasis is the main cause of death in malignant tumors patients, and also the barrier for its treatment. Exosomes, as extracellular vesicles carrying various functional molecules, participate in communication between cells or between cells and the microenvironment, and receive widespread attention because of its crucial role in regulating tumor metastasis. Myosin 1b is a kind of actin-based motors implicated in diverse cellular processes. It has been reported to be associated with a wide variety of human tumors and related to their poor prognosis. In pre-experiments, we found that myosin 1b is related to the metastasis of melanoma, and promotes the secretion of exosomes, but the exact underlying mechanisms of myosin 1b in melanoma metastasis and exosome regulation have not been fully elucidated. According to these, we propose the hypothesis that “myosin 1b promotes melanoma metastasis through regulating the secretion of exosomes”. By analyzing translocation of multivesicular body, and the function of myosin 1b mutants, screening for potential interacting proteins and using melanoma lung metastasis model, we will explore its underlying mechanism in melanoma metastasis and exosome secretion. This study is aimed at providing new molecular therapeutic targets for comprehensive treatment of melanoma.