Journal
ONCOGENE
Volume 30, Issue 44, Pages 4498-4508Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2011.154
Keywords
gastric carcinoma; IRX1; angiogenesis; vasculogenic mimicry; BDKRB2
Funding
- National Natural Science Foundation of China [30572127, 30770961, 30973486]
- Chinese National High Tech Program [863-2006AA02A402, 2006AA02A301]
- Shanghai Science and Technology Commission [09DZ1950101, 09JC1409600]
- Shanghai Charity Foundation for Cancer Research
Ask authors/readers for more resources
The overexpression of IRX1 gene correlates with the growth arrest in gastric cancer. Furthermore, overexpression of IRX1 gene suppresses peritoneal spreading and long distance metastasis. To explore the precise mechanisms, we investigated whether restoring IRX1 expression affects the angiogenesis or vasculogenic mimicry (VM). Human umbilical vein endothelial cells (HUVECs) and chick embryo and SGC-7901 gastric cancer cells were used for angiogenesis and VM analysis. Small interfering RNA was used for analyzing the function of BDKRB2, a downstream target gene of IRX1. As results, the remarkable suppression on peritoneal spreading and pulmonary metastasis of SGC-7901 cells by IRX1 transfectant correlates to reduced angiogenesis as well as VM formation. Using the supernatant from SGC-7901/ IRX1 cells, we found a strong inhibiting effect on angiogenesis both in vitro and in chick embryo. SGC-7901/IRX1 cells revealed strong inhibiting effect on VM formation too. By gene-specific RNA interference for BDKRB2, or its effector PAK1, we got an effective inhibition on tube formation, cell proliferation, cell migration and invasion in vitro. In conclusion, enforcing IRX1 expression effectively suppresses peritoneal spreading and pulmonary metastasis via anti-angiogenesis and anti-VM mechanisms, in addition to previously found cell growth and invasion. BDKRB2 and its downstream effector might be potential targets for anti-cancer strategy. Oncogene (2011) 30, 4498-4508; doi:10.1038/onc.2011.154; published online 23 May 2011
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available