RGS22 inhibits pancreatic adenocarcinoma cell migration through the G12/13 α subunit/F-actin pathway.
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.
Reproductive Medicine Center, Subei People's Hospital, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China.
Yanqiu
Y
Hu
Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
Jun
J
Xing
Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
Ling
L
Chen
Department of Histology and Embryology, Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China.
Ying
Y
Zheng
Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
Zuomin
Z
Zhou
D000199:Actins / Q000378:metabolism*; D000954:Antigens, Surface / Q000502:physiology*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D048430:Cell Shape; D020555:GTP-Binding Protein Regulators / Q000502:physiology*; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000502:physiology*; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000502:physiology
D000199:Actins; D000954:Antigens, Surface; D020555:GTP-Binding Protein Regulators; D008246:Lysophospholipids; D025521:Tumor Suppressor Proteins; C561241:regulator of G-protein signaling 22, human; D044365:GTP-Binding Protein alpha Subunits, G12-G13; C032881:lysophosphatidic acid