A Trio-Rac1-Pak1 signalling axis drives invadopodia disassembly

Yasmin Moshfegh, Jose Javier Bravo-Cordero, Veronika Miskolci, John Condeelis, Louis Hodgson

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

Rho family GTPases control cell migration and participate in the regulation of cancer metastasis. Invadopodia, associated with invasive tumour cells, are crucial for cellular invasion and metastasis. To study Rac1 GTPase in invadopodia dynamics, we developed a genetically encoded, single-chain Rac1 fluorescence resonance energy (FRET) transfer biosensor. The biosensor shows Rac1 activity exclusion from the core of invadopodia, and higher activity when invadopodia disappear, suggesting that reduced Rac1 activity is necessary for their stability, and Rac1 activation is involved in disassembly. Photoactivating Rac1 at invadopodia confirmed this previously unknown Rac1 function. We describe here an invadopodia disassembly model, where a signalling axis involving TrioGEF, Rac1, Pak1, and phosphorylation of cortactin, causes invadopodia dissolution. This mechanism is critical for the proper turnover of invasive structures during tumour cell invasion, where a balance of proteolytic activity and locomotory protrusions must be carefully coordinated to achieve a maximally invasive phenotype.

Original languageEnglish (US)
Pages (from-to)571-583
Number of pages13
JournalNature Cell Biology
Volume16
Issue number6
DOIs
StatePublished - Jun 2014

ASJC Scopus subject areas

  • Cell Biology

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