24 February 2019 : Laboratory Research
ADAR1 p110 Enhances Adhesion of Tumor Cells to Extracellular Matrix in Hepatocellular Carcinoma via Up-Regulating ITGA2 Expression
Jiajie Yu1BCE, Chunjun Zhang1BD, Qingsong Yu1DEF, Haibo Yu1AB, Bo Zhang1ADFG*DOI: 10.12659/MSM.911944
Med Sci Monit 2019; 25:1469-1479
Abstract
BACKGROUND: Intrahepatic and distant metastases could be the major cause of treatment failure in hepatocellular carcinoma (HCC). The deep mechanism of HCC metastasis is closely related to the interaction between integrins and extracellular matrix (ECM) in tumor microenvironment.
MATERIAL AND METHODS: In vitro cell adhesion assay was performed to determine the capability of adhering to ECM elements of HCC cells. To modulate the expression status of ADAR1 p110 in tumor cells, lentivirus system was applied. Meanwhile, patients’ HCC samples and orthotopic xenograft mouse model were used for verifying our in vitro data.
RESULTS: ADAR1 p110 could strongly enhance the adhesion of HCC tumor cells to ECM, which was usually regarded as the initiation of tumor invasion. Such phenotype was caused due to up-regulation of ITGA2 both in mRNA and protein level. Moreover, specimen collected from HCC patients revealed a positive correlation between ADAR1 and ITGA2. Finally, ADAR1 p110 promoted HCC metastasis was verified when we applied orthotopic xenograft mouse model.
CONCLUSIONS: ADAR1 could enhance HCC metastasis by promoting tumor cells adhering to ECM via increasing ITGA2 expression. This phenomenon could provide novel information to better understanding the mechanism of HCC metastasis procedure.
Keywords: Adenosine Deaminase, Carcinoma, Hepatocellular, Cell Adhesion Molecules, Integrin alpha2, Cell Adhesion, Extracellular Matrix, Liver Neoplasms, RNA, Messenger, RNA-Binding Proteins, transcriptional activation, tumor microenvironment
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