DRAM1与VAMP8相互作用调控自噬融合以促进肺癌细胞血管外渗的分子机制研究

肺癌是严重威胁人类健康的重要疾病之一，目前尚未有效的治疗方法。转移是导致肺癌患者的主要死亡原因，其中血管外渗是肺癌细胞转移到其他部位的重要途径。如何抑制肺癌细胞的血管外渗是亟需解决的科学问题。研究表明肺癌细胞的自噬活动与其外渗相关。我们发现DRAM1能够影响肺癌细胞的血管外渗，敲除DRAM1显著的抑制肺癌细胞血管外渗能力。进一步发现DRAM1与VAMP8相互作用促进自噬体与溶酶体的融合，且DRAM1调控VAMP8蛋白稳定性。据此推测：DRAM1通过促进VAMP8蛋白稳定性，继而增强自噬体与融合体的融合，使得提高肺癌细胞的血管外渗能力。本研究将围绕DRAM1对肺癌细胞的血管外渗能力的影响，探索DRAM1介导VAMP8蛋白稳定性在调控自噬体和溶酶体融合中的分子机制，从而揭示DRAM1对促进肺癌细胞血管外渗的机制。本研究结果将为自噬干预肺癌的转移治疗提供新的思路和手段。

Lung cancer are seriously threaten for human health，and there is no effective treatment for this disease. Metastasis is the main reason for causing death of lung cancer patient. How to inhibit the extravasation of lung cancer cells is a key scientific question. The evidence has shown that the lung cancer cell’autophagy activity promotes ability of vascular extravasation. We found that DRAM1 affects lung cancer cell’extravasation, and knockout DRAM1 significant inhibition of lung cancer cell’extravasation. We also found that DRAM1 modulates autophagosome fusion with lysosomes by interacting with VAMP8 and DRAM1 promotes stability of this protein. Therefore, we speculate that DRAM1 enhance the stability of VAMP8, which results in affecting autophagosome fusion with lysosomes, further to increase the lung cancer cell’extravasation. This study will focus on DRAM1 affecting lung cancer cell’ability in extravasation, to investigate the molecular mechanism of DRAM1 mediates VAMP8’protein stability in the regulation autophagsosome fusion with lysosomes, to identify DRAM1’function in promoting the lung cancer cell’extravasation. The results of this study will provide new ideas for the autophagy used for treatment with lung cancer’metastasis.