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Molecular Cancer
Published in: Molecular Cancer 1/2010

Open Access 01-12-2010 | Research

Prosaposin down-modulation decreases metastatic prostate cancer cell adhesion, migration, and invasion

Authors: Siyi Hu, Nathalie Delorme, Zhenzhen Liu, Tao Liu, Cruz Velasco-Gonzalez, Jone Garai, Ashok Pullikuth, Shahriar Koochekpour

Published in: Molecular Cancer | Issue 1/2010

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Abstract

Background

Factors responsible for invasive and metastatic progression of prostate cancer (PCa) remain largely unknown. Previously, we reported cloning of prosaposin (PSAP) and its genomic amplification and/or overexpression in several androgen-independent metastatic PCa cell lines and lymph node metastases. PSAP is the lysosomal precursor of saposins, which serve as activators for lysosomal hydrolases involved in the degradation of ceramide (Cer) and other sphingolipids.

Results

Our current data show that, in metastatic PCa cells, stable down-modulation of PSAP by RNA-interference via a lysosomal proteolysis-dependent pathway decreased β1A-integrin expression, its cell-surface clustering, and adhesion to basement membrane proteins; led to disassembly of focal adhesion complex; and decreased phosphorylative activity of focal adhesion kinase and its downstream adaptor molecule, paxillin. Cathepsin D (CathD) expression and proteolytic activity, migration, and invasion were also significantly decreased in PSAP knock-down cells. Transient-transfection studies with β1A integrin- or CathD-siRNA oligos confirmed the cause and effect relationship between PSAP and CathD or PSAP and Cer-β1A integrin, regulating PCa cell migration and invasion.

Conclusion

Our findings suggest that by a coordinated regulation of Cer levels, CathD and β1A-integrin expression, and attenuation of "inside-out" integrin-signaling pathway, PSAP is involved in PCa invasion and therefore might be used as a molecular target for PCa therapy.
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Metadata
Title
Prosaposin down-modulation decreases metastatic prostate cancer cell adhesion, migration, and invasion
Authors
Siyi Hu
Nathalie Delorme
Zhenzhen Liu
Tao Liu
Cruz Velasco-Gonzalez
Jone Garai
Ashok Pullikuth
Shahriar Koochekpour
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2010
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-9-30

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