1. WNT11 is a direct target of early growth response protein 1
- Author
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Euitaek Jung, Hyunjin Yeo, Sung Shin Ahn, Soon Young Shin, Jeong Yeon Lee, Young Han Lee, Jeong Kon Seo, and JuHwan Kim
- Subjects
MAPK/ERK pathway ,endocrine system ,animal structures ,Transcription, Genetic ,MAP Kinase Kinase 4 ,MAP Kinase Signaling System ,p38 mitogen-activated protein kinases ,Early growth response 1 ,Breast Neoplasms ,Biology ,p38 Mitogen-Activated Protein Kinases ,Biochemistry ,Article ,03 medical and health sciences ,Cell Line, Tumor ,Tumor Microenvironment ,Tumor necrosis factor α ,Wnt family member 11 ,Humans ,Promoter Regions, Genetic ,Wnt Signaling Pathway ,Molecular Biology ,Transcription factor ,5'-regulatory region ,Early Growth Response Protein 1 ,0303 health sciences ,Tumor microenvironment ,Binding Sites ,Tumor Necrosis Factor-alpha ,Kinase ,030302 biochemistry & molecular biology ,JNK Mitogen-Activated Protein Kinases ,Wnt signaling pathway ,General Medicine ,Mitogen-activated protein kinase ,Wnt Proteins ,Tumor progression ,Colonic Neoplasms ,embryonic structures ,Cancer research ,Female ,Ectopic expression ,sense organs ,Mitogen-Activated Protein Kinases ,Protein Binding ,Signal Transduction - Abstract
WNT11 is a member of the non-canonical Wnt family and plays a crucial role in tumor progression. However, the regulatory mechanisms underlying WNT11 expression are unclear. Tumor necrosis factor-alpha (TNFα) is a major inflammatory cytokine produced in the tumor microenvironment and contributes to processes associated with tumor progression, such as tumor invasion and metastasis. By using site-directed mutagenesis and introducing a serial deletion in the 5'-regulatory region of WNT11, we observed that TNFα activates the early growth response 1 (EGR1)-binding sequence (EBS) in the proximal region of WNT11 and that the transcription factor EGR1 is necessary for the TNFα-induced transcription of WNT11. EGR1 bound directly to the EBSs within the proximal 5'-regulatory region of WNT11 and ectopic expression of EGR1 stimulated WNT11 promoter activity, whereas the knockdown of EGR1 expression by RNA interference reduced TNFα-induced WNT11 expression in T47D breast cancer cells. We also observed that mitogen-activated protein kinases (MAPK), extracellular signalregulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 kinase mediated TNFα-induced transcription of WNT11 via EGR1. Our results suggest that EGR1 directly targets WNT11 in response to TNFα stimulation in breast cancer cells. [BMB Reports 2020; 53(12): 628-633].
- Published
- 2020
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