RGS22 inhibits pancreatic adenocarcinoma cell migration through the G12/13 α subunit/F-actin pathway

Abstract Pancreatic cancer is characterized by the potential for local invasion, allowing it to spread during the early developmental stages of the disease. Regulator of G protein signaling 22 (RGS22) localizes to the cytoplasm in pancreatic adenocarcinoma tissue. We overexpressed RGS22 in the human pancreatic cancer cell line BXPC-3. Cells that overexpressed RGS22 had much lower wound-healing rates and greatly reduced migration compared to the control cells. Conversely, cells in which RGS22 expression had been downregulated had higher wound-healing rates and migration than the control cells. These results confirmed that RGS22 expression suppresses pancreatic adenocarcinoma cell migration. Pull-down and coimmunoprecipitation assays revealed that RGS22 had specific interactions with the heterotrimeric G protein G12 α subunit (GNA12) and GNA13 in the cells. We also demonstrated that in the presence of higher RGS22 expression, the cell deformation and F-actin formation caused by lysophosphatidic acid treatment, is delayed. Constitutively active Gα subunits did not accelerate GTP hydrolysis to GDP. We did not investigate the function of RGS22 as a negative regulator of heterotrimeric G12/13 protein signaling. Our data demonstrate that RGS22 acts as a tumor suppressor, repressing human pancreatic adenocarcinoma cell migration by coupling to GNA12/13, which in turn leads to inhibition of stress fiber formation.