Kisspeptin-10 (Kp-10), a decapeptide derived from the primary translation product of KISS1 gene, has been previously reported to be a key hormone for puberty and an inhibitor for tumor metastasis via the activation of G protein-coupled receptor 54 (Gpr54). However, whether Kp-10 inhibits angiogenesis, which is critical for tumor growth and metastasis and other human diseases, is still unknown. Here we demonstrate that Kp-10 significantly inhibits human umbilical vein endothelial cell (HUEVC) migration, invasion, and tube formation, key processes in angiogenesis. Using chicken chorioallantoic membrane (CAM) assay and VEGF-induced mouse corneal micropocket assay, we demonstrate that Kp-10 inhibits angiogenesis in vivo. Furthermore, Kp-10 inhibits tumor growth in SCID mice xenografted with human prostate cancer cells (PC-3) through inhibiting tumor angiogenesis while Kp-10 has little effect on the proliferation of HUVECs and human prostate cancer cells. In deciphering the underlying molecular mechanisms, we demonstrate that Kp-10 suppresses VEGF expression by inhibiting the binding of Sp1 to VEGF promoter and by blocking the activation of c-Src/FAK and Rac/Cdc42 signaling pathway in HUVECs, leading to the inhibition of tumor angiogenesis.
BackgroundThe genes of plants can be up- or down-regulated during viral infection to influence the replication of viruses. Identification of these differentially expressed genes could shed light on the defense systems employed by plants and the mechanisms involved in the adaption of viruses to plant cells. Differential gene expression in Nicotiana benthamiana plants in response to infection with Bamboo mosaic virus (BaMV) was revealed using cDNA-amplified fragment length polymorphism (AFLP).ResultsFollowing inoculation with BaMV, N. benthamiana displayed differential gene expression in response to the infection. Isolation, cloning, and sequencing analysis using cDNA-AFLP furnished 90 cDNA fragments with eight pairs of selective primers. Fifteen randomly selected genes were used for a combined virus-induced gene silencing (VIGS) knockdown experiment, using BaMV infection to investigate the roles played by these genes during viral infection, specifically addressing the means by which these genes influence the accumulation of BaMV protein. Nine of the 15 genes showed either a positive or a negative influence on the accumulation of BaMV protein. Six knockdown plants showed an increase in the accumulation of BaMV, suggesting that they played a role in the resistance to viral infection, while three plants showed a reduction in coat protein, indicating a positive influence on the accumulation of BaMV in plants. An interesting observation was that eight of the nine plants showing an increase in BaMV coat protein were associated with cell rescue, defense, death, aging, signal transduction, and energy production.ConclusionsThis study reports an efficient and straightforward method for the identification of host genes involved in viral infection. We succeeded in establishing a cDNA-AFLP system to help track changes in gene expression patterns in N. benthamiana plants when infected with BaMV. The combination of both DNA-AFLP and VIGS methodologies made it possible to screen a large number of genes and identify those associated with infections of plant viruses. In this report, 9 of the 15 analyzed genes exhibited either a positive or a negative influence on the accumulation of BaMV in N. benthamiana plants.
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