title: Differences in association of the serine/threonine protein phosphatase PP-2A with microtubules of metastatic and nonmetastatic tumor cells.
abstract: Motility and adhesiveness are regulated by a multitude of factors, including cytoskeletal polymerization and phosphorylation of cytoskeletal and associated proteins. The metastatic Lewis lung carcinoma variant, LLC-LN7, was highly motile in vitro and had lower levels of the serine/threonine protein phosphatase PP-2A than did the nonmetastatic variant, LLC-C8. Reducing PP-2A activity of the nonmetastatic cells pharmacologically or with catalytic (Calpha) subunit antisense increased their in vitro motility. Nonmetastatic LLC-C8 cells had a greater proportion of polymerized tubulin which co-purified with PP-2A as compared to the metastatic LLC-LN7 cells. The PP-2A that was associated with the microtubules of these cells showed similar ratios of the Aalpha structural subunit to the Calpha/beta catalytic subunits. In contrast, the proportion of the regulatory subunit B56alpha was lower in the nonmetastatic LLC-C8 cells as compared to the metastatic LLC-LN7 cells. These studies show the role of PP-2A in restricting the motility of nonmetastatic tumor cells and suggest that the loss of this regulatory control in metastatic LLC-LN7 cells may be due to both a reduction in microtubule-associated PP-2A and a difference in the composition of the subunits of PP-2A that is associated with the microtubules.
authors.affiliation: Research Services, Hines VA Hospital, Illinois 60141, USA. myoung1@luc.edu
authors.forename: M R
authors.initials: MR
authors.lastname: Young
authors.forename: S W
authors.initials: SW
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Meisinger
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000378:metabolism* / Q000473:pathology*; D002465:Cell Movement; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D009362:Neoplasm Metastasis; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D014404:Tubulin; D010749:Phosphoprotein Phosphatases