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Differences in association of the serine/threonine protein phosphatase PP-2A with microtubules of metastatic and nonmetastatic tumor cells

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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 (Cα) 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 Aα structural subunit to the Cα/β catalytic subunits. In contrast, the proportion of the regulatory subunit B56α 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.

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Authors and Affiliations

  1. Research Services, Hines V.A. Hospital, Hines, Illinois

    M. Rita I. Young & Shirley W. Liu

  2. Departments of Pathology and Otolaryngology, Loyola University Medical Center, Maywood, Illinois, USA

    Jeremy Meisinger

Authors
  1. M. Rita I. Young
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  2. Shirley W. Liu
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  3. Jeremy Meisinger
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Young, M.R.I., Liu, S.W. & Meisinger, J. Differences in association of the serine/threonine protein phosphatase PP-2A with microtubules of metastatic and nonmetastatic tumor cells. Clin Exp Metastasis 18, 407–413 (2000). https://doi.org/10.1023/A:1010934106651

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  • DOI: https://doi.org/10.1023/A:1010934106651

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