Protein phosphatases-1 and -2A regulate tumor cell migration, invasion and cytoskeletal organization.
The role of protein kinase A (PKA) and protein phosphatases (PP) -1 and -2A in regulating the metastatic phenotype of Lewis lung carcinoma (LLC) cells was evaluated. The metastatic LLC-LN7 cells were more motile and invasive than were nonmetastatic LLC-C8 cells. Compared to the nonmetastatic cells, the LLC-LN7 cells had increased PKA activity and a deficiency in PP-2A. Nonmetastatic LLC-C8 cells became migratory and invasive when PP-1 and P-2A activities were inhibited with okadaic acid. This stimulation of LLC-C8 motility was tempered by PKA inhibition. Also examined was if the okadaic acid-stimulated LLC-C8 motility was associated with a change in the cytoskeletal organization to that typical of metastatic cells. Treatment of nonmetastatic LLC-C8 cells with okadaic acid caused a redistribution of F-actin toward the periphery of the cells, and eventually to a loss of the filamentous actin network. All of these effects were reversed upon removal of okadaic acid. Our results show that PP-1/2A maintain reduced motility and increased cytoskeletal organization within nonmetastatic LLC cells.
Young
M R
MR
Research Service (151-Z2) Hines V.A. Hospital, IL 60141, USA.
D000199:Actins / Q000032:analysis; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000201:enzymology / Q000473:pathology*; D002465:Cell Movement; D017868:Cyclic AMP-Dependent Protein Kinases / Q000032:analysis; D003599:Cytoskeleton / Q000648:ultrastructure*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000199:Actins; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D019319:Okadaic Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases