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WNT11 is a direct target of early growth response protein 1.


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 (TNF?) 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 TNF? 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 TNF?-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 TNF?-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 TNF?-induced transcription of WNT11 via EGR1. Our results suggest that EGR1 directly targets WNT11 in response to TNF? stimulation in breast cancer cells. [BMB Reports 2020; 53(12): 628-633].

SUBMITTER: Kim J 

PROVIDER: S-EPMC7781917 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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WNT11 is a direct target of early growth response protein 1.

Kim JuHwan J   Jung Euitaek E   Ahn Sung Shin SS   Yeo Hyunjin H   Lee Jeong Yeon JY   Seo Jeong Kon JK   Lee Young Han YH   Shin Soon Young SY  

BMB reports 20201201 12


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 observe  ...[more]

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