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

V. Astro, C. Asperti, G. Cangi, C. Doglioni, I. De Curtis

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1841-1849
Number of pages9
JournalOncogene
Volume30
Issue number15
DOIs
Publication statusPublished - Apr 14 2011

Fingerprint

Cell Movement
Extracellular Matrix
Breast Neoplasms
Cell Count
Cortactin
Pseudopodia
RNA Interference
Transfection
Neoplasms
Podosomes
Genes
Proteins

Keywords

  • cell migration
  • invadopodia
  • invasion
  • lamellipodia
  • liprins

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Liprin-α1 regulates breast cancer cell invasion by affecting cell motility, invadopodia and extracellular matrix degradation. / Astro, V.; Asperti, C.; Cangi, G.; Doglioni, C.; De Curtis, I.

In: Oncogene, Vol. 30, No. 15, 14.04.2011, p. 1841-1849.

Research output: Contribution to journalArticle

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