title: F-box protein FBXL2 inhibits gastric cancer proliferation by ubiquitin-mediated degradation of forkhead box M1.
abstract: F-box/LRR-repeat protein 2 (FBXL2), a component of Skp-Cullin-F box (SCF) ubiquitin E3 ligase, has been shown to inhibit tumorigenesis by targeting and ubiquitinating several oncoproteins. However, its role in gastric cancer remains poorly understood. Here, by tandem mass spectrometry, we show that FBXL2 interacts with forkhead box M1 (FoxM1) transcription factor. As a result, FBXL2 promotes ubiquitination and degradation of FoxM1 in gastric cancer cells. Furthermore, overexpression of FBXL2 inhibits, while its deficiency promotes cell proliferation and invasion. Expression levels of cell-cycle regulators (Cdc25B and p27), which are down-stream target effectors of FoxM1, are also regulated by FBXL2. Therefore, our results uncover a previous unknown network involving FBXL2 and FoxM1 in the regulation of gastric cancer growth.
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Liang-qing
authors.initials: LQ
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Dun
authors.initials: D
authors.lastname: Pan
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Wen-jun
authors.initials: WJ
authors.lastname: Xie
mesh_terms: D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D017353:Gene Deletion; D055785:Gene Knockdown Techniques; D006801:Humans; D047468:Immunoprecipitation; D009361:Neoplasm Invasiveness; D059748:Proteolysis; D034741:RNA, Small Interfering / Q000235:genetics; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology*; D013379:Substrate Specificity; D053719:Tandem Mass Spectrometry; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D044783:F-Box Proteins; C122028:FBXL2 protein, human; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D034741:RNA, Small Interfering; D025801:Ubiquitin; D044843:SKP Cullin F-Box Protein Ligases
keywords: F-box/LRR-repeat protein 2; forkhead box M1; gastric cancer; growth; ubiquitination