β-catenin/TCF4 is required for DDX17-induced epithelial-mesenchymal transition and metastasis in hepatocellular carcinoma

This study, led by researchers from the Research Center for Preclinical Medicine of Southwest Medical University, focuses on exploring the functional roles and molecular mechanisms of DDX17 in HCC metastasis. Hepatocellular carcinoma (HCC) is a highly malignant tumor with high incidence and mortality, and metastasis is a major obstacle to improving patient survival.

The research team first found that DDX17 is overexpressed in HCC tissues compared with non-cancerous tissues, and its high expression is significantly associated with tumor invasion, metastasis, and clinical staging of HCC patients. Through in vitro cell experiments, they demonstrated that knocking down DDX17 can reduce the migration and invasion abilities of HCC cells, while overexpressing DDX17 has the opposite effect. In an orthotopic HCC nude mouse model, silencing DDX17 significantly reduced metastatic lesions, further confirming the role of DDX17 in promoting HCC metastasis.

Epithelial-mesenchymal transition (EMT) is a key process for tumor cells to acquire migration and invasion capabilities. The study found that DDX17 can induce EMT in HCC cells, as evidenced by changes in the expression of epithelial markers (such as E-cadherin) and mesenchymal markers (such as N-cadherin, Snail, and Vimentin).

Mechanistically, the researchers discovered that transcription factor TCF4 directly binds to the promoter region of DDX17 and enhances its transcription. Moreover, DDX17 can promote the nuclear translocation of β-catenin, and this process depends on its helicase functional domain. In the nucleus, β-catenin forms a complex with TCF4, which in turn enhances the transcription of DDX17, forming a regulatory loop. Importantly, the β-catenin/TCF4 complex is essential for DDX17-induced migration, invasion, and EMT of HCC cells.

"Our study reveals a novel DDX17-driven pathway in HCC metastasis, highlighting its potential as a therapeutic target to halt malignant progression. Additionally, our center are mainly working on EMT and cancer metastasis" said by Dr. Junjiang Fu.

Dr. Chaoxiang Lv, the other corresponding author, added, "The β-catenin/TCF4/DDX17 feedback loop provides a mechanistic foundation for understanding HCC dissemination and opens avenues for targeted intervention."

See the article: 

DDX17 promotes hepatocellular carcinoma metastasis through β-catenin/TCF4 pathway

https://doi.org/10.1002/mog2.70039