Uterine corpus endometrial carcinoma (UCEC) is a common malignancy in the female reproductive system, associated with high morbidity and mortality. Despite the high prevalence of UCEC, molecular understanding of uterine… Click to show full abstract
Uterine corpus endometrial carcinoma (UCEC) is a common malignancy in the female reproductive system, associated with high morbidity and mortality. Despite the high prevalence of UCEC, molecular understanding of uterine endothelium tumorigenesis remains poorly understood. In this study, we reported that transcription factor 21 (TCF21) inhibits cancer cell proliferation and invasion following overexpression, in vitro and in vivo. Moreover, in response to hypoxia, TCF21 is highly expressed in UCEC cells carrying wild-type p53, and is transcriptional target of p53. We observed that TCF21 interferes with the MAP kinase pathway, which is supported by a substantially reduced level of phosphorylated mitogen-activated protein kinase 1 (MAPK1 or ERK) in cells expressing a higher level of TCF21. Furthermore, we identified the specific region of TCF21 that is responsible for its interaction with mitogen-activated protein kinase 1 (MEK) and a subsequently reduced activity of ERK. Using molecular docking and mutagenes...
               
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