title: B-cell translocation gene 3 overexpression inhibits proliferation and invasion of colorectal cancer SW480 cells via Wnt/β-catenin signaling pathway.
abstract: Increasing evidences have shown that B-cell translocation gene 3 (BTG3) inhibits metastasis of multiple cancer cells. However, the role of BTG3 in colorectal cancer (CRC) and its possible mechanism have not yet been reported. In our study, we evaluated BTG3 expression in several CRC cell lines. Then, pcDNA3.1-BTG3 was transfected into SW480 cells. We found that BTG3 was upregulated in SW480 cells after overexpression plasmid transfection. BTG3 overexpression significantly inhibited cell growth and decreased PCNA (proliferating cell nuclear antigen) and Ki67 levels. BTG3 overexpression markedly downregulated Cyclin D1 and Cyclin E1 levels, whereas elevated p27. Overexpression of BTG3 arrested the cell cycle at G1 phase, which was abrogated by p27 silencing. Furthermore, migration, invasion and EMT of SW480 cells were significantly suppressed by BTG3 overexpression. Further investigations showed the inhibition of Wnt/β-catenin signaling pathway. We then used GSK3β specific inhibitor SB-216763 to activate the Wnt/β-catenin signaling pathway. We found that Wnt/β-catenin signaling pathway activation reversed the effect of BTG3 overexpression on cell proliferation, cell cycle progression, invasion and EMT. In conclusion, BTG3 overexpression inhibited cell growth, induced cell cycle arrest and suppressed the metastasis of SW480 cells via the Wnt/β-catenin signaling pathway. BTG3 may be considered as a therapeutic target in CRC treatment.
authors.forename: D
authors.initials: D
authors.lastname: Mao
authors.forename: L
authors.initials: L
authors.lastname: Qiao
authors.forename: H
authors.initials: H
authors.lastname: Lu
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
mesh_terms: D018938:Caco-2 Cells; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000473:pathology*; D019938:Cyclin D1 / Q000096:biosynthesis; D019927:Cyclin E / Q000096:biosynthesis; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D019394:Ki-67 Antigen / Q000378:metabolism; D008301:Maleimides / Q000494:pharmacology; D009361:Neoplasm Invasiveness / Q000473:pathology; D015513:Oncogene Proteins / Q000096:biosynthesis; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics*
chemical_list: C424522:BTG3 protein, human; C530104:CCND1 protein, human; C475820:CCNE1 protein, human; D018797:Cell Cycle Proteins; D019927:Cyclin E; D007211:Indoles; D019394:Ki-67 Antigen; D008301:Maleimides; D015513:Oncogene Proteins; D018809:Proliferating Cell Nuclear Antigen; D011506:Proteins; D034741:RNA, Small Interfering; C417521:SB 216763; C413374:p27 antigen; D019938:Cyclin D1; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta
keywords: BTG3; SB-216762; Wnt/β-catenin signaling pathway.; colorectal cancer; metastasis; p27