定量蛋白质组学分析鉴定出参与乳腺癌细胞迁移的FOXM1新效应因子。
Quantitative proteomic analysis identifies new effectors of FOXM1 involved in breast cancer cell migration.
作者信息
Ye Xiaojuan, Zhang Yi, He Bin, Meng Yuesheng, Li Yandong, Gao Yong
机构信息
Department of Oncology, East Hospital, Tongji University School of Medicine Shanghai 200120, China.
Department of Oncology, East Hospital, Dalian Medical University Shanghai 200120, China.
出版信息
Int J Clin Exp Pathol. 2015 Dec 1;8(12):15836-44. eCollection 2015.
The Forkhead Box M1 (FOXM1) transcription factor plays important roles in tumorigenesis and tumor metastasis in multiple human carcinomas. However, the underlying mechanisms for FOXM1 function remain to be classified. In the present study, we employed quantitative proteomic approach to search new downstream targets of FOXM1 in breast cancer MDA-MB-231 cells. A total of 4125 proteins were identified and quantified by label-free quantitation, of which 318 proteins were significantly changed (with P-value <0.05) between FOXM1 knockdown cells and control cells. Among them, three proteins ACSL4, CGGBP1 and PGRMC2 were significantly downregulated with FOXM1 reduction by western blot analysis. Further functional assays revealed that knockdown of the three proteins in MDA-MB-231 cells attenuated the ability of cell migration, consistent with the phenotype of FOXM1 knockdown. These results suggest that new potential downstream effectors of FOXM1 were identified by proteomic approach, and may provide new potential therapeutic targets in breast cancer.
叉头框M1（FOXM1）转录因子在多种人类癌症的肿瘤发生和肿瘤转移中发挥重要作用。然而，FOXM1功能的潜在机制仍有待分类。在本研究中，我们采用定量蛋白质组学方法在乳腺癌MDA-MB-231细胞中寻找FOXM1的新下游靶点。通过无标记定量法共鉴定和定量了4125种蛋白质，其中318种蛋白质在FOXM1敲低细胞和对照细胞之间有显著变化（P值<0.05）。其中，通过蛋白质印迹分析，随着FOXM1减少，三种蛋白质ACSL4、CGGBP1和PGRMC2显著下调。进一步的功能分析表明，MDA-MB-231细胞中这三种蛋白质的敲低减弱了细胞迁移能力，这与FOXM1敲低的表型一致。这些结果表明，通过蛋白质组学方法鉴定了FOXM1的新潜在下游效应物，可能为乳腺癌提供新的潜在治疗靶点。
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