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Liprin-α1 regulates breast cancer cell invasion by affecting cell motility, invadopodia and extracellular matrix degradation

Oncogene volume 30, pages 1841–1849 (2011)Cite this article

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A Corrigendum to this article was published on 14 April 2011

Abstract

Migration of cells and degradation of the extracellular matrix (ECM) are required for efficient tumor cell invasion, but the underlying molecular mechanisms are only partially known. The PPFIA1 gene for liprin-α1 is frequently amplified in human breast cancers. We recently demonstrated that liprin-α1 is an important regulator of cell edge dynamics during motility. We show, herein, that the liprin-α1 protein is highly expressed in human breast tumors. Functional analysis shows that liprin-α1 is specifically required for the migration and invasion of highly invasive human breast cancer MDA-MB-231 cells. We used time-lapse analysis to demonstrate defects in the motility of liprin-α1-depleted cells that include a striking instability of the lamellipodia. Liprin-α1 levels altered by either RNA interference or overexpression affected also cell spreading and the number of invadopodia per cell, but not the density of invadopodia per unit of surface area. On the other hand, silencing of liprin-α1 inhibited the degradation of the ECM, whereas its overexpression enhanced degradation, resulting in significant negative or positive effects, respectively, on the area of degradation per invadopodium. Transfection of fluorescent-labeled cortactin revealed that depletion of liprin-α1 also affected the assembly and disassembly of invadopodia, with decrease of their lifetime. Our results strongly support a novel important role of liprin-α1 in the regulation of human tumor cell invasion.

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Acknowledgements

Support to I de Curtis by the AIRC (Italian Association for Cancer Research, grant no. 5060) and by the Italian Telethon Foundation (grant no. GGP09078) is gratefully acknowledged. The plasmid for DsRed-Cortactin was generously provided by Mark A McNiven (Mayo Clinic, Rochester, MN, USA). We thank Cesare Covino of the Alembic facility at our Institute for his support in the morphological analysis, Rosanna Latino and Maurizio Ferrari for the cytogenetic analysis, and Jacopo Meldolesi for critical reading of the manuscript.

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Authors and Affiliations

  1. Division of Neurosciences, Cell Adhesion Unit, San Raffaele Scientific Institute and San Raffaele University, Milano, Italy

    V Astro, C Asperti & I de Curtis

  2. Pathology Unit, San Raffaele Scientific Institute and San Raffaele University, Milano, Italy

    G Cangi & C Doglioni

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  1. V Astro
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  2. C Asperti
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Correspondence to I de Curtis.

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Supplementary Information accompanies the paper on the Oncogene website

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Astro, V., Asperti, C., Cangi, G. et al. Liprin-α1 regulates breast cancer cell invasion by affecting cell motility, invadopodia and extracellular matrix degradation. Oncogene 30, 1841–1849 (2011). https://doi.org/10.1038/onc.2010.562

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