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 cyto-skeleton. 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

Molecular mechanisms of the antimetastatic activity of nuclear clusterin in prostate cancer cells / Moretti, R. M.; S., Mai; M., Montagnani Marelli; Rizzi, Federica Maria Angela; Bettuzzi, Saverio; P., Limonta. - In: INTERNATIONAL JOURNAL OF ONCOLOGY. - ISSN 1019-6439. - 39:(2011), pp. 225-234. [10.3892/ijo.2011.1030]

Molecular mechanisms of the antimetastatic activity of nuclear clusterin in prostate cancer cells

RIZZI, Federica Maria Angela;BETTUZZI, Saverio;
2011-01-01

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 cyto-skeleton. 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
2011
Molecular mechanisms of the antimetastatic activity of nuclear clusterin in prostate cancer cells / Moretti, R. M.; S., Mai; M., Montagnani Marelli; Rizzi, Federica Maria Angela; Bettuzzi, Saverio; P., Limonta. - In: INTERNATIONAL JOURNAL OF ONCOLOGY. - ISSN 1019-6439. - 39:(2011), pp. 225-234. [10.3892/ijo.2011.1030]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2370698
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