Nuclear localization of TEF3-1 promotes cell cycle progression and angiogenesis in cancer
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Kaixuan Teng1,*, Cuilan Deng1,*, Jie Xu1, Qiuxu Men1, Tao Lei1, Da Di1, Ting Liu2, Wenhua Li2, Xin Liu1
1Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, College of Pharmacy, Wuhan University, Wuhan, 430071, P.R. China
2College of Life Sciences, Wuhan University, Wuhan, 430072, P.R. China
*These authors contributed equally to this work
Xin Liu, e-mail: [email protected]
Keywords: transcription enhancer factor 3 isoform 1, angiogenesis, cell cycle, HUVEC, cancer therapy
Received: November 09, 2015 Accepted: January 29, 2016 Published: February 12, 2016
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.
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