title: FBXW7 negatively regulates ENO1 expression and function in colorectal cancer.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Shandong, P.R. China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Zhan
authors.affiliation: Department of Anatomy and Key Laboratory of Experimental Teratology, Ministry of Education, Shandong University School of Medicine, Shandong, P.R. China.
authors.forename: Yuli
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Shandong, P.R. China.
authors.forename: Shihu
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Shandong, P.R. China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Anatomy and Key Laboratory of Experimental Teratology, Ministry of Education, Shandong University School of Medicine, Shandong, P.R. China.
authors.forename: Yunshan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Anatomy and Key Laboratory of Experimental Teratology, Ministry of Education, Shandong University School of Medicine, Shandong, P.R. China.
authors.forename: Mingxin
authors.initials: M
authors.lastname: Wen
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Mao
authors.affiliation: Department of Anatomy and Key Laboratory of Experimental Teratology, Ministry of Education, Shandong University School of Medicine, Shandong, P.R. China.
authors.forename: Guangwei
authors.initials: G
authors.lastname: Wei
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Shandong, P.R. China.
authors.forename: Pengju
authors.initials: P
authors.lastname: Zhang
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D044783:F-Box Proteins / Q000378:metabolism*; D000073979:F-Box-WD Repeat-Containing Protein 7; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D013058:Mass Spectrometry; D010751:Phosphopyruvate Hydratase / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012044:Regression Analysis; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase