Delta-Like Homolog 2 Facilitates Malignancy of Hepatocellular Carcinoma via Activating EGFR/PKM2 Signaling Pathway.

Autor: Liu X; Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu Province, People's Republic of China., Li T; Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu Province, People's Republic of China., Wang Y; Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu Province, People's Republic of China., Gao X; Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu Province, People's Republic of China., Wang F; Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, People's Republic of China., Chen Y; School of Life Science, Xuzhou Medical University, Xuzhou, Jiangsu Province, People's Republic of China., Wang K; Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, People's Republic of China., Luo W; Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, People's Republic of China., Kong F; Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu Province, People's Republic of China., Kou Y; Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu Province, People's Republic of China., You H; Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu Province, People's Republic of China., Kong D; Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu Province, People's Republic of China., Zhang Q; Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu Province, People's Republic of China., Tang R; Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu Province, People's Republic of China.
Jazyk: angličtina
Zdroj: Molecular carcinogenesis [Mol Carcinog] 2025 Jan; Vol. 64 (1), pp. 176-191. Date of Electronic Publication: 2024 Oct 28.
DOI: 10.1002/mc.23836
Abstrakt: Delta-like homolog 2 (DLK2) plays a crucial role in adipogenesis, chondrogenic differentiation, and the progression of certain cancers. However, the key roles of DLK2 underlying the progression of hepatocellular carcinoma (HCC) remain ambiguous. In the current study, we demonstrate that DLK2 is upregulated in HCC, significantly correlated with clinicopathological variables and serves as an independent diagnostic marker. Functional assays reveal that DLK2 facilitates malignant progression of HCC in vitro and in vivo models. Mechanistically, DLK2 binds to EGFR resulting in its auto-phosphorylation, which activates NF-κB pathway leading to P65-dependent transcriptional upregulation of PKM2. Furthermore, that elevates both enzyme-dependent and -independent activities of PKM2 contributing to cancer proliferation and metastasis. In summary, our findings demonstrate a novel pro-tumoral role and mechanism of DLK2 in the regulation of HCC malignant progression, suggesting its potential as a clinical diagnostic marker and therapeutic target.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
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