A Trio-Rac1-Pak1 signalling axis drives invadopodia disassembly.

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

Research output: Contribution to journalArticle

64 Citations (Scopus)

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)574-586
Number of pages13
JournalNature Cell Biology
Volume16
Issue number6
DOIs
StatePublished - 2014

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Biosensing Techniques
Cortactin
Neoplasm Metastasis
Neoplasms
rho GTP-Binding Proteins
Fluorescence Resonance Energy Transfer
GTP Phosphohydrolases
Podosomes
Cell Movement
Phosphorylation
Phenotype

ASJC Scopus subject areas

  • Cell Biology

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A Trio-Rac1-Pak1 signalling axis drives invadopodia disassembly. / Moshfegh, Yasmin; Bravo-Cordero, Jose Javier; Miskolci, Veronika; Condeelis, John S.; Hodgson, Louis.

In: Nature Cell Biology, Vol. 16, No. 6, 2014, p. 574-586.

Research output: Contribution to journalArticle

Moshfegh, Yasmin ; Bravo-Cordero, Jose Javier ; Miskolci, Veronika ; Condeelis, John S. ; Hodgson, Louis. / A Trio-Rac1-Pak1 signalling axis drives invadopodia disassembly. In: Nature Cell Biology. 2014 ; Vol. 16, No. 6. pp. 574-586.
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