TY - JOUR T1 - FBXW7 negatively regulates ENO1 expression and function in colorectal cancer. JF - Lab Invest Y1 - 2015 A1 - Zhan, Panpan A1 - Wang, Yuli A1 - Zhao, Shihu A1 - Liu, Chunyan A1 - Wang, Yunshan A1 - Wen, Mingxin A1 - Jiang-Hua Mao A1 - Wei, Guangwei A1 - Zhang, Pengju KW - Biomarkers, Tumor KW - Blotting, Western KW - Cell Cycle Proteins KW - Colorectal Neoplasms KW - DNA Primers KW - DNA-Binding Proteins KW - Electrophoresis, Gel, Two-Dimensional KW - F-Box Proteins KW - Gene Expression Regulation, Neoplastic KW - HCT116 Cells KW - Humans KW - Immunohistochemistry KW - Mass Spectrometry KW - Phosphopyruvate Hydratase KW - Real-Time Polymerase Chain Reaction KW - Regression Analysis KW - Tumor Suppressor Proteins KW - Ubiquitin-Protein Ligases AB -

FBXW7 (F-box and WD40 domain protein 7) is a tumor suppressor frequently inactivated in human cancers. The precise molecular mechanisms by which FBXW7 exerts antitumor activity remain under intensive investigation and are thought to relate in part to FBXW7-mediated destruction of key cancer-relevant proteins. Enolase 1 (ENO1) possesses oncogenic activity and is often overexpressed in various human cancers, besides its critical role in glycolysis. However, the detailed regulatory mechanisms of ENO1 expression remain unclear. Here we show that the elevated expression of ENO1 was identified in FBXW7-depletion HCT116 cells through two-dimensional protein electrophoresis and mass spectrometry assays (2DE-MS). Subsequent western blotting and immunohistochemical assays confirmed that ENO1 expression reversely correlates with FBXW7 expression in several cells and colon cancer tissues. Furthermore, we show that FBXW7 physically binds to ENO1 and targets ENO1 for ubiquitin-mediated degradation. Functionally, we found that FBXW7 suppresses the ENO1-induced gene expression, lactate production, cell proliferation and migration. These findings suggest that ENO1 is a novel substrate of FBXW7, and its activity can be negatively regulated by FBXW7 at the posttranslational level. Our work provides a novel molecular insight into FBXW7-directed tumor suppression through regulation of ENO1.

VL - 95 IS - 9 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26097998?dopt=Abstract ER -