Abstract
It has been discovered that hepatocellular carcinoma (HCC) has high ability of migration and angiogenesis. This study aimed to explore the mechanism of HCC cell migration and angiogenesis. BEL-7402 cell line was used as HCC cell model for investigating the regulation of cell migration upon c-Src inhibitors (PP2 and SU6656) treatment. Western blot was used for detecting the expression of MT1-MMP and VEGF-C. The activity of MMP2 and MMP9 was monitored with gelatin zymography assay. BEL-7402 cell migration and invasion was detected by wound healing assay and Transwell. Immunoprecipitation was used for detecting the interaction among c-Src, pro-MT1-MMP, Furin and VEGF-C. Our results have show that the expression of MT1-MMP and VEGF-C were inhibited by PP2 and SU6656, in accordance with c-Src activity. Zymography assay demonstrated that the activity of MMP2 and MMP9 decreased upon PP2 or SU6656 treatment. The invasion and migration of BEL-7402 were inhibited. We also found that c-Src interacted with Furin in vivo . The interaction between Furin and its substrates pro-MT1-MMP、pro-VEGF-C decreased upon c-Src inhibitors treatment. These findings indicate that the activity of c-Src inhibition associated with cell invasion and migration decreased by down-regulating the interaction between Furin and its substrates (pro-MT1-MMP, pro-VEGF-C). Keywords: Hepatocellular carcinoma (HCC), Furin, c-Src inhibitor, MT1-MMP, VEGF-C, cell migration. African Journal of Biotechnology Vol 13(12), 1423-1429
Highlights
Hepatocellular carcinoma (HCC) is the leading cause of cancer- related death in the world, which has a high potential ability of metastasis in tumor progression (GLOBOCAN, 2008)
We investigate whether Furin is regulated by platelet derived growth factor-BB (PDGF-BB) through c-Src kinase and how Furin activity is controlled to mediate the processing of its substrate MT1MMP and VEGF-C
The ability of invasion and migration of the cells treated with PP2 or SU6656 decreased significantly compared with the control (Figure 1)
Summary
Hepatocellular carcinoma (HCC) is the leading cause of cancer- related death in the world, which has a high potential ability of metastasis in tumor progression (GLOBOCAN, 2008). The underlying mechanisms of HCC initiation, progression and metastasis are still not fully understood (Tang et al, 2010). Furin is the best-characterized representative of the mammalian subtilisin-like family of proprotein convertase. It is synthesized as inactive proenzyme and rapidly matured by autocatalytic cleavage between the prodomain and the catalytic domain in endoplasmic reticulum (ER). (Vey et al, 1994)
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