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 Gprotein signaling22 (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 Gprotein G12 αsubunit (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.