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Int. J. Mol. Sci. 2017, 18(3), 500; doi:10.3390/ijms18030500

The Expression and Functional Significance of Runx2 in Hepatocellular Carcinoma: Its Role in Vasculogenic Mimicry and Epithelial–Mesenchymal Transition

1
Department of Pathology, Tianjin Medical University, Tianjin 300070, China
2
Department of Pathology, General Hospital of Tianjin Medical University, Tianjin 300052, China
3
Department of Pathology, Cancer Hospital of Tianjin Medical University, Tianjin 300060, China
*
Author to whom correspondence should be addressed.
Academic Editor: Li Yang
Received: 4 January 2017 / Revised: 20 February 2017 / Accepted: 21 February 2017 / Published: 27 February 2017
(This article belongs to the Special Issue Tumor Microenvironment and Metabolism)
View Full-Text   |   Download PDF [32589 KB, uploaded 27 February 2017]   |  

Abstract

The transcription factor Runx2 has been reported to promote epithelial-mesenchymal transition (EMT) in many tumors. Vasculogenic mimicry (VM) is described as the mimicry of endothelial cells by tumor cells to form microvascular tubes in aggressive tumors. Galectin-3 has been reported to regulate cell invasion, migration, and VM formation; it could be regulated by Runx2. However, the relationship between Runx2, Galectin-3, EMT, and VM has not been studied in hepatocellular carcinoma (HCC). We examined Runx2 expression in 89 human HCC samples and found Runx2 expression was associated with VM. Clinical-pathological data analysis revealed that Runx2 expression was associated with a shorter survival period. Overexpression of Runx2 promoted EMT and enhanced cell migration, invasion, and VM formation in HepG2 cells. Conversely, the downregulation of Runx2 inhibited EMT and reduced cell invasion, migration, and VM formation in SMMC7721. Galectin-3 expression declined following the downregulation of Runx2 in HepG2 cells, and increased in SMMC7721 cells after Runx2 knockdown. We consistently demonstrated that the downregulation of LGALS3 in HepG2-Runx2 cells reduced cell migration; invasion and VM formation; while upregulation of LGALS3 in SMMC7721-shRunx2 cells enhanced cell migration, invasion, and VM formation. The results indicate that Runx2 could promote EMT and VM formation in HCC and Galectin-3 might have some function in this process. View Full-Text
Keywords: Runx2; Galectin-3; epithelial-mesenchymal transition; vasculogenic mimicry; portal vein invasion; hepatocellular carcinoma Runx2; Galectin-3; epithelial-mesenchymal transition; vasculogenic mimicry; portal vein invasion; hepatocellular carcinoma
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Cao, Z.; Sun, B.; Zhao, X.; Zhang, Y.; Gu, Q.; Liang, X.; Dong, X.; Zhao, N. The Expression and Functional Significance of Runx2 in Hepatocellular Carcinoma: Its Role in Vasculogenic Mimicry and Epithelial–Mesenchymal Transition. Int. J. Mol. Sci. 2017, 18, 500.

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