DDX56 promotes EMT and cancer stemness via MELK-FOXM1 axis in hepatocellular carcinoma

Autor: Qing Li, Tianyi Wang, Ximin Wang, XinYu Ge, Tao Yang, Wei Wang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: iScience, Vol 27, Iss 6, Pp 109827- (2024)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2024.109827
Popis: Summary: Hepatocellular carcinoma (HCC) is a major global cause of death, with epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)-like properties contributing to its metastasis. DEAD box helicase 56 (DDX56) is involved in carcinogenesis, but its role in EMT induction and stem phenotype maintenance is unclear. This study assessed the impact of DDX56 absence on HCC cell stemness and EMT. DDX56 was found to be overexpressed in HCC tissues, correlating with disease stage and prognosis. In vitro, DDX56 stimulated tumor cell proliferation, migration, invasion, EMT, and stemness. It also enhanced maternal embryonic leucine-zipper kinase (MELK)-mediated forkhead box protein M1 (FOXM1) expression, regulating cancer stemness and malignant traits. In vivo, DDX56 knockdown in tumor-bearing mice reduced tumorigenicity and lung metastasis by modulating the MELK-FOXM1 signaling pathway. Collectively, DDX56 initiates stem cell-like traits in HCC and promotes EMT via MELK-FOXM1 activation, shedding light on HCC pathogenesis and suggesting a potential anti-cancer therapeutic target.
Databáze: Directory of Open Access Journals