Rac activation and inactivation control plasticity of tumour cell movement

Vicky Sanz Moreno, Gilles Gadea, Jessica Ahn, Hugh Paterson, Pierfrancesco Marra, Sophie Pinner, Erik Sahai, Christopher J. Marshall

Research output: Contribution to journalArticlepeer-review

766 Citations (Scopus)


Tumor cells exhibit two different modes of individual cell movement. Mesenchymal-type movement is characterized by an elongated cellular morphology and requires extracellular proteolysis. In amoeboid movement, cells have a rounded morphology, are less dependent on proteases, and require high Rho-kinase signaling to drive elevated levels of actomyosin contractility. These two modes of cell movement are interconvertible. We show that mesenchymal-type movement in melanoma cells is driven by activation of the GTPase Rac through a complex containing NEDD9, a recently identified melanoma metastasis gene, and DOCK3, a Rac guanine nucleotide exchange factor. Rac signals through WAVE2 to direct mesenchymal movement and suppress amoeboid movement through decreasing actomyosin contractility. Conversely, in amoeboid movement, Rho-kinase signaling activates a Rac GAP, ARH-GAP22, that suppresses mesenchymal movement by inactivating Rac. We demonstrate tight interplay between Rho and Rac in determining different modes of tumor cell movement, revealing how tumor cells switch between different modes of movement.

Original languageEnglish
Pages (from-to)510-523
Number of pages14
Issue number3
Publication statusPublished - 31 Oct 2008


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