候选抑癌基因VPS33B与CCDC19直接相互作用抑制非小细胞肺癌生长和转移

前期生物信息学预测、qPCR验证了VPS33B在非小细胞肺癌（NSCLC）中表达下调, 在NSCLC中通过抑制PI3K/AKT信号通路发挥候选抑癌基因作用，能体外抑制细胞生长、游走和侵袭。酵母双杂交及外源性免疫共沉淀实验显示， VPS33B可能为NSCLC抑癌候选基因CCDC19直接作用蛋白。因此我们推测VPS33B与CCDC19直接相互作用，从而抑制NSCLC生长和转移。进一步工作：明确VPS33B在NSCLC中发挥了抑癌基因作用及其分子机制；明确CCDC19在NSCLC转移中的作用和机制；确认VPS33B与CCDC19在NSCLC中直接相互作用；明确VPS33B与CCDC19在NSCLC中协同调节PI3K/AKT及其下游关键信号通路从而抑制NSCLC生长和转移。我们的工作将首次揭示VPS33B在NSCLC中的作用和机制，并确定其与CCDC19相互作用，共同参与抑制NSCLC发病过程。

In previous investigation, we used bioinformatics and qPCR to validate the downregulated expression of VPS33B in NSCLC. Preliminary analysis of function and molecular basis indicated that VPS33B acted as a tumor suppressor through suppressing PI3K/AKT signal and inhibited cell growth, migration, and invasion in NSCLC. Interestingly, our recent study showed that CCDC19, a tumor suppressor in NSCLC, was identified as a candidate protein directly interacting with VPS33B using yeast two-hybrid and exogenous co-immunoprecipitation assays. The further works are as followed: 1) Identifying VPS33B as a tumor suppressor and the detailed molecular basis in NSCLC. Confirming the role and molecular basis of CCDC19 in NSCLC metastasis; 2) Confirming the direct interaction of VPS33B with CCDC19 in NSCLC. 3) Validating the direct interaction of VPS33B with CCDC19 that synergistically modulate PI3K/AKT and its downstream signals suppressing cell growth and metastasis in NSCLC. Our work will be the first to reveal the roles and mechanisms of VPS33B in NSCLC and will determine its interaction with CCDC19 which co-participate in the inhibition for NSCLC pathogenesis.