Molecular mechanisms of the antimetastatic activity of nuclear clusterin in prostate cancer cells
Articolo
Data di Pubblicazione:
2011
Citazione:
Molecular mechanisms of the antimetastatic activity of nuclear clusterin in prostate cancer cells / R.M. Moretti, S. Mai, M. Montagnani Marelli, F. Rizzi, S. Bettuzzi, P. Limonta. - In: INTERNATIONAL JOURNAL OF ONCOLOGY. - ISSN 1019-6439. - 39:1(2011), pp. 225-234. [10.3892/ijo.2011.1030]
Abstract:
The proapoptotic activity of nuclear clusterin (nCLU) in cancer cells is now well established. We previously showed that nCLU decreases the motility of prostate cancer cells by triggering a dramatic dismantling of the actin cytoskeleton. Here, we sought to unravel the molecular mechanisms of the antimetastatic activity of nCLU. We found that nCLU i) decreases LIMK1 expression, thus increasing the levels of the active (unphosphorylated) form of cofilin, the well known actin depolymerizing factor; ii) binds to vimentin, sequestering the protein from its adhesion sites at the cell periphery, thus interfering with its role in cell motility and adhesion; iii) affects the intracellular distribution of E-cadherin (the major component of epithelial adherens junctions) which appears to be diffusely distributed in the cells. Through these mechanisms nCLU reduces the migratory/invasive behavior of PC3 cells; this effect is further demonstrated by a decreased secretion of active MMP-2 from the cells. Thus, in addition to its proapoptotic function, nCLU also exerts a strong anti-migratory/anti-invasive activity in prostate cancer cells, by interfering with the cytoskeletal components and by decreasing MMP-2 activity.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
nuclear clusterin ; cell motility ; cell invasion ; prostate cancer ; cytoskeleton
Elenco autori:
R.M. Moretti, S. Mai, M. Montagnani Marelli, F. Rizzi, S. Bettuzzi, P. Limonta
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