Protein geranylgeranylation (GGylation) is an important biochemical process for 
many cellular signaling molecules. Previous studies have shown that GGylation is 
essential for cell survival in many types of cancer. However, the molecular 
mechanism mediating the cell survival effect remains elusive. In this report, we 
show that the Hippo pathway mediates GGylation-dependent cell proliferation and 
migration in breast cancer cells. Blockade of GGylation enhanced phosphorylation 
of Mst1/2 and Lats1, and inhibited YAP and TAZ activity and the Hippo-YAP/TAZ 
pathway-dependent transcription. The effect of GGylation blockade on inhibition 
of breast cancer cell proliferation and migration is dependent on the 
Hippo-YAP/TAZ signaling, in which YAP appears to regulate cell proliferation and 
TAZ to regulate cell migration. Furthermore, GGylation-dependent cell 
proliferation is correlated with the activity of YAP/TAZ in breast cancer cells. 
Finally, Gγ and RhoA are the GGylated proteins that may transduce GGylation 
signals to the Hippo-YAP/TAZ pathway. Taken together, our studies have 
demonstrated that the Hippo-YAP/TAZ pathway is essential for GGylation-dependent 
cancer cell proliferation and migration.