Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Analytical Chemistry and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Sci Rep. 2017 Oct 31;7(1):14460. doi: 10.1038/s41598-017-14453-2.
Forkhead box protein 3 (FOXP3) is implicated in tumor progression and prognosis in various types of tumor cells. We have recently reported that FOXP3 inhibited proliferation of gastric cancer (GC) cells through activating the apoptotic signaling pathway. In this study, we found that over-expression of FOXP3 inhibited GC cell migration, invasion and proliferation. Then, the label-free quantitative proteomic approach was employed to further investigating the down-stream proteins regulated by FOXP3, resulting in a total of 3,978 proteins quantified, including 186 significantly changed proteins. Caveolin-1 (CAV1), as a main constituent protein of caveolae, was one of those changed proteins up-regulated in FOXP3-overexpressed GC cells, moreover, it was assigned as one of the node proteins in the protein-protein interaction network and the key protein involved in focal adhesion pathway by bioinformatics analysis. Further biological experiments confirmed that FOXP3 directly bound to the promoter regions of CAV1 to positively regulate CAV1 transcription in GC cells. In summary, our study suggested that FOXP3 can be considered as a tumor suppressor in GC via positively regulating CAV1 through transcriptional activation, and this FOXP3-CAV1 transcriptional regulation axis may play an important role in inhibiting invasion and metastasis of GC cells. Data are available via ProteomeXchange under identifier PXD007725.
叉头框蛋白 3（FOXP3）参与多种肿瘤细胞的肿瘤进展和预后。我们最近报道，FOXP3 通过激活凋亡信号通路抑制胃癌（GC）细胞的增殖。在这项研究中，我们发现 FOXP3 的过表达抑制 GC 细胞的迁移、侵袭和增殖。然后，我们采用无标记定量蛋白质组学方法进一步研究 FOXP3 调节的下游蛋白，共定量了 3978 种蛋白，其中包括 186 种明显变化的蛋白。窖蛋白-1（CAV1）作为小窝的主要组成蛋白之一，是 FOXP3 过表达 GC 细胞中上调的变化蛋白之一，此外，通过生物信息学分析，它被分配为蛋白质-蛋白质相互作用网络中的节点蛋白之一，并且是参与粘着斑途径的关键蛋白。进一步的生物学实验证实，FOXP3 可直接结合 CAV1 启动子区域，从而在 GC 细胞中正向调节 CAV1 转录。综上所述，我们的研究表明，FOXP3 可通过转录激活正向调节 CAV1 ，从而被视为 GC 中的肿瘤抑制因子，并且该 FOXP3-CAV1 转录调节轴可能在抑制 GC 细胞侵袭和转移中发挥重要作用。数据可通过 ProteomeXchange 以标识符 PXD007725 获取。
