| First Author | Li Y | Year | 2018 |
| Journal | Exp Cell Res | Volume | 370 |
| Issue | 2 | Pages | 373-382 |
| PubMed ID | 29966664 | Mgi Jnum | J:268499 |
| Mgi Id | MGI:6271231 | Doi | 10.1016/j.yexcr.2018.06.039 |
| Citation | Li Y, et al. (2018) ADAM17 promotes cell migration and invasion through the integrin beta1 pathway in hepatocellular carcinoma. Exp Cell Res 370(2):373-382 |
| abstractText | ADAM17 is believed to promote tumor development by facilitating both cell proliferation and migration. In this study, we investigated the involvement of ADAM17 and the activation of the integrin pathway in the regulation of the malignant properties of hepatocellular carcinoma cells and tissues. ADAM17 was positively correlated with active integrin beta1, which was determined using a human tissue microarray and an N-nitrosodiethylamine-induced HCC mouse model. We found elevated ADAM17 and active integrin beta1 levels in HCC tissues compared with adjacent liver tissues, and the active integrin beta1 levels were associated with tumor size and TNM grade. High ADAM17 and active integrin beta1 levels in tumor tissues were significantly associated with poor survival of HCC patients. RNAi-mediated ADAM17 knockdown and integrin beta1 blockade significantly attenuated the migration and invasion of HCC cells, and overexpression of ADAM17 showed the reverse effects. ADAM17 interference attenuated the intrahepatic growth and metastasis of HCC cells in an orthotopic xenograft model. ADAM17-knockdown cells showed diminished levels of active integrin beta1, p-FAK, p-AKT, MMP-2 and MMP-9. ADAM17 knockdown significantly attenuated the translocation of the Notch1 intracellular domain into the nucleus, whereas overexpression of the Notch1 intracellular domain rescued the translocation and enhanced the activation of integrin beta1. Our data provide evidence for ADAM17 as an important determinant of malignant properties via regulation of integrin beta1 activation and Notch1 signaling. Inhibition of ADAM17 may provide viable therapeutic potential for preventing HCC metastasis. |
