title: Nuclear localization of TEF3-1 promotes cell cycle progression and angiogenesis in cancer.
abstract: TEF3-1 (transcriptional enhancer factor 3 isoform 1), also known as TEAD4 (TEA domain family member 4), was recently revealed as an oncogenic character in cancer development. However, the underlying molecular pathogenic mechanisms remain undefined. In this paper, we investigated nuclear TEF3-1 could promote G1/S transition in HUVECs, and the expression levels of cyclins and CDKs were upregulated. Additionally, if TEF3-1 was knocked down, the expression of cyclins and CDKs was downregulated while the expression of P21, a negative regulator of the cell cycle, was upregulated. A microarray analysis also confirmed that TEF3-1 overexpression upregulates genes that are related to cell cycle progression and the promotion of angiogenesis. Moreover, we observed that nuclear TEF3-1 was highly expressed during the formation of vascular structures in gastric cancer (GC). Finally, tumor xenograft experiments indicated that, when TEF3-1 was knocked down, tumor growth and angiogenesis were also suppressed. Taken together, these results demonstrate for the first time that TEF3-1 localization to the nucleus stimulates the cell cycle progression in HUVECs and specifically contributes to tumor angiogenesis. Nuclear TEF3-1 in HUVECs may serve as an oncogenic biomarker, and the suppression of TEF3-1 may be a potential target in anti-tumor therapy.
authors.affiliation: Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, College of Pharmacy, Wuhan University, Wuhan, 430071, P.R. China.
authors.forename: Kaixuan
authors.initials: K
authors.lastname: Teng
authors.affiliation: Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, College of Pharmacy, Wuhan University, Wuhan, 430071, P.R. China.
authors.forename: Cuilan
authors.initials: C
authors.lastname: Deng
authors.affiliation: Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, College of Pharmacy, Wuhan University, Wuhan, 430071, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, College of Pharmacy, Wuhan University, Wuhan, 430071, P.R. China.
authors.forename: Qiuxu
authors.initials: Q
authors.lastname: Men
authors.affiliation: Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, College of Pharmacy, Wuhan University, Wuhan, 430071, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Lei
authors.affiliation: Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, College of Pharmacy, Wuhan University, Wuhan, 430071, P.R. China.
authors.forename: Da
authors.initials: D
authors.lastname: Di
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, 430072, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, 430072, P.R. China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Li
authors.affiliation: Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, College of Pharmacy, Wuhan University, Wuhan, 430071, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D000091262:TEA Domain Transcription Factors; C486309:TEAD4 protein, human; D014157:Transcription Factors
keywords: HUVEC; angiogenesis; cancer therapy; cell cycle; transcription enhancer factor 3 isoform 1