乳腺癌膜转移通道的鉴定及机制研究

远处转移是乳腺癌死亡的主要原因，转移新途径的探索是肿瘤研究领域的核心科学问题。申请人在长期研究细胞膜及骨架蛋白的基础上发现乳腺癌中存在一种由质膜构成的中空管状结构（Tube-like vessel），肿瘤细胞包裹其中且与乳腺癌远处转移显著相关（Nature, submitted），测序发现ESR1，MAP3K1和PIK3R1与其生成相关，我们推测Tube-like vessel可能是乳腺癌远处转移的独立途径。本研究拟首先通过体外实验模拟Tube-like vessel的生成和肿瘤细胞的转移，然后利用高通量测序、蛋白质组学等手段探索调控Tube-like vessel的驱动基因，再通过动物模型研究Tube-like vessel的转移机理和阻断途径，最后前瞻性临床试验验证此科学假说。本研究将初步证实Tube-like vessel新的肿瘤转移途径，为乳腺癌转移理论及治疗策略提供新思路。

Distant metastasis is the main cause of death of breast cancer, and the exploration of new ways of metastasis is the core scientific problem in the field of oncology research. In the previous work, we found that there was an extracellular membrane compartment (Tube-like vessel) composed of plasma membrane in breast cancer, which was encapsulated by tumor cells and significantly related to distant metastasis of breast cancer (Nature, submitted). RNA-seq showed that ESR1,MAP3K1 and PIK3R1 were related to the production of Tube-like vessel, so we speculated that Tube-like vessel may be an independent pathway of distant metastasis of breast cancer. In this study, we first simulate the formation of Tube-like vessel and metastasis of tumor cells in vitro, then explore the driving genes that regulate Tube-like vessel by means of high-throughput sequencing and proteomics, and then establish an animal model of tumor metastasis to study the metastasis mechanism and blocking pathway of Tube-like vessel. Finally, prospective clinical trials are used to verify this scientific hypothesis. This study will initially confirm the existence of a new tumor metastasis pathway of Tube-like vessel, and provide new ideas for the improvement of breast cancer metastasis theory and treatment strategy.