LEF1 Enhances the Progression of Colonic Adenocarcinoma via Remodeling the Cell Motility Associated Structures.

Li Xiao,Yang Feng,Chenshuang Jia,Wei Duan,Yingchun Hou,Qian Gao,Xuewei Zhao,Caixia Zhang,Lirong Chen,Ruixia Zhao,Xinyao Li,Jie Xu,Zhan Shu,Sinan Cheng,Zheng Lu,Yue Yuan,Guochao Nie

doi:10.3390/ijms221910870

Abstract

Lymphoid enhancer-binding factor 1 (LEF1) is a key transcription factor mediating the Wnt signaling pathway. LEF1 is a regulator that is closely associated with tumor malignancy and is usually upregulated in cancers, including colonic adenocarcinoma. The underlying molecular mechanisms of LEF1 regulation for colonic adenocarcinoma progression remain unknown. To explore it, the LEF1 expression in caco2 cells was inhibited using an shRNA approach. The results showed that downregulation of LEF1 inhibited the malignancy and motility associated microstructures, such as polymerization of F-actin, β-tubulin, and Lamin B1 in caco2 cells. LEF1 inhibition suppressed the expression of epithelial/endothelial-mesenchymal transition (EMT) relevant genes. Overall, the current results demonstrated that LEF1 plays a pivotal role in maintaining the malignancy of colonic adenocarcinoma by remodeling motility correlated microstructures and suppressing the expression of EMT-relevant genes. Our study provided evidence of the roles LEF1 played in colonic adenocarcinoma progression, and suggest LEF1 as a potential target for colonic adenocarcinoma therapy.

Highlights

Colonic adenocarcinoma is one of the leading causes of cancer-associated mortality from the digestive system [1,2]
The results suggest that Lymphoid enhancer-binding factor 1 (LEF1) might play a carcinogenic role in colonic adenocarcinoma
LEF1 expression may contribute to cancer development [26,27,28], but there is a lack of evidence to support malignant phenotype changes, especially motility-associated microstructure changes, such as remodeling of lamellipodia/filopodia based on F-actin/β-tubulin polymerization

Summary

Introduction

Colonic adenocarcinoma is one of the leading causes of cancer-associated mortality from the digestive system [1,2]. Due to improved diagnostic and therapeutic strategies, as well as decreased societal risk factor exposure, the incidence rate of colonic adenocarcinoma has been steadily decreasing. The survival rate for colonic adenocarcinoma remains unsatisfactory [3]. The oncogenesis and progression of cancer involves multiple genetic mutations. The molecular mechanisms and key regulators of colonic adenocarcinoma progression and metastasis remain elusive and need to be investigated. Further exploration of the molecular mechanisms is essential to improve current diagnostic and treatment strategies for colonic adenocarcinoma

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Results

Discussion

Conclusion