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.
Highlights
Transcription Enhancer Factor 3 Isoform 1 (TEF3-1), known as TEA Domain Family Member 4 (TEAD4) (TEA domain family member 4), belongs to a class of transcription factors, which are all widely expressed in eukaryotic cells
After the Human Umbilical Vein Endothelial Cells (HUVEC) were infected with the Flag-tagged lentivirus, the protein levels of TEF3-1 and TEF3-1ΔNLS were examined by western blot analysis with antibodies against TEF3-1 or Flag; these antibodies recognize the tags that were fused with full-length TEF3-1 and TEF3-1ΔNLS, in which the nuclear location sequence (NLS) was deleted, respectively
TEF3-1 changed the morphology of HUVECs, which became more elongated than normal cells
Summary
TEF3-1 (transcriptional enhancer factor 3 isoform 1), known as TEAD4 (TEA domain family member 4), belongs to a class of transcription factors, which are all widely expressed in eukaryotic cells This transcription factor was found to bind to the MCAT motif of gene promoters [1, 2]. This gene product is a member of the transcriptional enhancer factor (TEF) family of transcription factors, which contain the TEA/ATTS DNAbinding domain. It is called related transcriptional enhancer factor 1 (RTEF-1), transcription factor 13like 1 (TCF13 L1), and related transcription enhancer factor 1B (hRTEF-1B). As a negative regulator of the YAP-TEAD transcriptional complex, VGL might be a new tumor suppressor target in the treatment of lung cancer [12, 13]
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