ELK3 Mediated by ZEB1 Facilitates the Growth and Metastasis of Pancreatic Carcinoma by Activating the Wnt/β-Catenin Pathway

Qiuyan Zhao; Qiuyan Zhao; Yingchun Ren; Yingchun Ren; Haoran Xie; Haoran Xie; Lanting Yu; Lanting Yu; Jiawei Lu; Jiawei Lu; Weiliang Jiang; Wenqin Xiao; Zhonglin Zhu; Rong Wan; Rong Wan; Baiwen Li; Baiwen Li

ELK3 Mediated by ZEB1 Facilitates the Growth and Metastasis of Pancreatic Carcinoma by Activating the Wnt/β-Catenin Pathway

2021

Rapid progression and metastasis are the major causes of death in patients with pancreatic ductal adenocarcinoma (PDAC). ELK3, a member of the ternary complex factor (TCF), has been associated with the initiation and progression of various cancers. However, the role of ELK3 in PDAC is not yet fully understood. Online databases and immunohistochemistry were used to analyze the ELK3 levels in PDAC tissues. The function of ELK3 was confirmed by a series of in vivo and in vitro studies. Western blotting and immunofluorescence were used to detect the molecular mechanisms of PDAC. ChIP-qPCR was used to study the mechanism responsible for the elevation of ELK3 expression in PDAC. The ELK3 levels were higher in PDAC tissues than in adjacent normal tissues. Functionally, we demonstrated that ELK3 acted as an oncogene to promote PDAC tumorigenesis and metastasis. Further study suggested that ELK3 promoted PDAC cell migration and invasion by activating the Wnt/β-catenin pathway, and proved that ZEB1 could directly bind to the promoter of ELK3 to increase its transcription. Finally, both were associated with the patients’ clinicopathological features and worse overall survival. Conclusively, our findings enrich the role of ELK3 in PDAC, and provide potential avenues for exploring more effective biomarkers and therapeutic strategies for the treatment of PDAC.

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