Mri. Young et al., Differences in association of the serine/threonine protein phosphatase PP-2A with microtubules of metastatic and nonmetastatic tumor cells, CLIN EXP M, 18(5), 2001, pp. 407-413
Motility and adhesiveness are regulated by a multitude of factors, includin
g cytoskeletal polymerization and phosphorylation of cytoskeletal and assoc
iated proteins. The metastatic Lewis lung carcinoma variant, LLC-LN7, was h
ighly motile in vitro and had lower levels of the serine/threonine protein
phosphatase PP-2A than did the nonmetastatic variant, LLC-C8. Reducing PP-2
A activity of the nonmetastatic cells pharmacologically or with catalytic (
C alpha) subunit antisense increased their in vitro motility. Nonmetastatic
LLC-C8 cells had a greater proportion of polymerized tubulin which co-puri
fied 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 A alpha structural subunit to the C alpha/beta catalytic subunits. I
n contrast, the proportion of the regulatory subunit B56 alpha 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 nonme
tastatic tumor cells and suggest that the loss of this regulatory control i
n metastatic LLC-LN7 cells may be due to both a reduction in microtubule-as
sociated PP-2A and a difference in the composition of the subunits of PP-2A
that is associated with the microtubules.