Geranylgeranylation promotes proliferation, migration and invasion of gastric cancer cells through the YAP signaling pathway

Geranylgeranylation (GGylation) is a lipid modification process of signaling proteins. Currently, very little is known about the GGylation signaling for gastric cancer cell proliferation and migration. In this report, we found that inhibition of GGylation by the mevalonate pathway inhibitor atorvastatin and the geranylgeranyltransferase I inhibitor GGTI-298 impairs proliferation and migration of the gastric cancer AGS cells. During searching the signal ing pathway for the effect, we observed that YAP, a transcription activator and downstream effector of the hippo pathway, was suppressed by inhibition of GGylation, as evaluated by detection of the mRNA level of its known target genes CYR61 and CTGF and translocation to nuclei. Knockdown of YAP by shRNAs produced a similar effect on proliferation and migration of gastric cancer AGS cells to that of GGylation inhibition, suggesting that GGylation signaling promotes gastric cancer cell proliferation and migration by activation of YAP. Our studies provide a potential new therapeutic targeting pathway for gastric cancer.