Downregulation of ADAM10 Expression Inhibits Metastasis and Invasiveness of Human Hepatocellular Carcinoma HepG2 Cells

Abstract

Objective. This study aims to investigate the effects of ADAM10 expression on metastasis and invasiveness of human hepatocellular carcinoma HepG2 cells. Methods. The HepG2 cells were transfected with medium only, the empty vector, the control siRNA, or siRNA against ADAM10, respectively. Cell migration assay and Transwell invasiveness assay were performed to detect the effects of ADAM10 knockdown on migration and invasiveness of HepG2 cells. Western blotting and real-time RT PCR were performed to investigate the effects of knock-down of ADAM10 on protein and mRNA levels of E-cadherin gene. Results. Cell migration and invasiveness of HepG2 cells transfected with ADAM10 siRNA were significantly decreased, when compared with the cells transfected with the control siRNA, suggesting that the downregulation of ADAM10 expression inhibits cell migration and invasiveness. The Western blotting results suggest that the down-regulation of ADAM10 expression increases E-cadherin protein levels. The real-time RT-PCR results indicated that the mRNA level of E-cadherin is not detectably affected by the knock-down of ADAM10 gene. Conclusions. Expression of ADAM10 may be related to cell migration and invasiveness of human hepatocellular carcinoma HepG2 cells via a mechanism related to E-cadherin.

Knockout of ADAM10 enhances sorafenib antitumor activity of hepatocellular carcinoma in vitro and in vivo

“…Consistent with these findings, our recent results showed that ADAM10 is overexpressed in HCC tissues and there were significant associations between the protein levels of ADAM10 and tumor grade, amount of tumor differentiation, tumor size and the presence of metastasis (22). In addition, the RNA interference (RNAi)-mediated downregulation of endogenous ADAM10 was found to decrease the cell migration and invasion of HCC (23). Yang et al found that ADAM10 plays an important role in modulating the chemosensitivity of HCC cells to doxorubicin (24).…”

miR-365 targets ADAM10 and suppresses the cell growth and metastasis of hepatocellular carcinoma

“…Our previous study showed that ADAM10 expression was significantly upregulated in HCC tissues, and was significantly associated with tumor grade, tumor size and lymph node metastasis (25). Recently, several studies have shown that downregulation of ADAM10 inhibited HCC cell migration and invasion (22,26), and increased sorafenib sensitivity in HCC cells (27). These results suggest that ADAM10 functions as an oncogene in HCC.…”

Effects of ADAM10 upregulation on progression, migration, and prognosis of nasopharyngeal carcinoma

“…Previous studies have shown that ADAM10 is overexpressed in a variety of cancers such as hepatocellular carcinoma, oral squamous cell carcinoma, melanoma, lung cancers, pancreatic carcinoma, gastric cancer, and bladder cancer . Accumulating evidence has also shown that ADAM10 exerts an important role in cancer pathogenesis, progression, chemoresistance, metastasis, and invasion by several different mechanisms . Activation of positively stimulating pathways is arguably the most important of all the mechanisms .…”

“…(11)(12)(13)(14)(15)(16)(17)(18) Accumulating evidence has also shown that ADAM10 exerts an important role in cancer pathogenesis, progression, chemoresistance, metastasis, and invasion by several different mechanisms. (7,8,11,13,(19)(20)(21)(22)(23) Activation of positively stimulating pathways is arguably the most important of all the mechanisms. (24) Moreover, ADAM10-mediated shedding of adhesion proteins also results in increased cell proliferation.…”