Profilin1 regulates invadopodium maturation in human breast cancer cells

A. Valenzuela-Iglesias, Ved P. Sharma, B. T. Beaty, Z. Ding, L. E. Gutierrez-Millan, P. Roy, John S. Condeelis, J. J. Bravo-Cordero

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Invadopodia are actin-driven membrane protrusions that show oscillatory assembly and disassembly causing matrix degradation to support invasion and dissemination of cancer cells in vitro and in vivo. Profilin1, an actin and phosphoinositide binding protein, is downregulated in several adenocarcinomas and it is been shown that its depletion enhances invasiveness and motility of breast cancer cells by increasing PI(3,4)P2 levels at the leading edge. In this study, we show for the first time that depletion of profilin1 leads to an increase in the number of mature invadopodia and these assemble and disassemble more rapidly than in control cells. Previous work by Sharma et al. (2013a), has shown that the binding of the protein Tks5 with PI(3,4)P2 confers stability to the invadopodium precursor causing it to mature into a degradation-competent structure. We found that loss of profilin1 expression increases the levels of PI(3,4)P2 at the invadopodium and as a result, enhances recruitment of the interacting adaptor Tks5. The increased PI(3,4)P2-Tks5 interaction accelerates the rate of invadopodium anchorage, maturation, and turnover. Our results indicate that profilin1 acts as a molecular regulator of the levels of PI(3,4)P2 and Tks5 recruitment in invadopodia to control the invasion efficiency of invadopodia.

Original languageEnglish (US)
Pages (from-to)78-89
Number of pages12
JournalEuropean Journal of Cell Biology
Volume94
Issue number2
DOIs
StatePublished - Feb 1 2015

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Keywords

  • Matrix degradation
  • PI(3,4)P(2)
  • Profilin1
  • Tks5

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

Cite this

Valenzuela-Iglesias, A., Sharma, V. P., Beaty, B. T., Ding, Z., Gutierrez-Millan, L. E., Roy, P., Condeelis, J. S., & Bravo-Cordero, J. J. (2015). Profilin1 regulates invadopodium maturation in human breast cancer cells. European Journal of Cell Biology, 94(2), 78-89. https://doi.org/10.1016/j.ejcb.2014.12.002