Article abstract
Nature Cell Biology 11, 257 - 268 (2009)
Published online: 8 February 2009 | doi:10.1038/ncb1833
Myocardin-related transcription factors and SRF are required for cytoskeletal dynamics and experimental metastasis
Souhila Medjkane1,3, Cristina Perez-Sanchez1,4, Cedric Gaggioli2, Erik Sahai2 & Richard Treisman1
Abstract
Rho GTPases control cytoskeletal dynamics through cytoplasmic effectors and regulate transcriptional activation through myocardin-related transcription factors (MRTFs), which are co-activators for serum response factor (SRF). We used RNA interference to investigate the contribution of the MRTF–SRF pathway to cytoskeletal dynamics in MDA-MB-231 breast carcinoma and B16F2 melanoma cells, in which basal MRTF–SRF activity is Rho-dependent. Depletion of MRTFs or SRF reduced cell adhesion, spreading, invasion and motility in culture, without affecting proliferation or inducing apoptosis. MRTF-depleted tumour cell xenografts showed reduced cell motility but proliferated normally. Tumour cells depleted of MRTF or SRF failed to colonize the lung from the bloodstream, being unable to persist after their arrival in the lung. Only a few genes show MRTF-dependent expression in both cell lines. Two of these, MYH9 (NMHCIIa) and MYL9 (MLC2), are also required for invasion and lung colonization. Conversely, expression of activated MAL/MRTF-A increases lung colonization by poorly metastatic B16F0 cells. Actin-based cell behaviour and experimental metastasis thus require Rho-dependent nuclear signalling through the MRTF–SRF network.
- Transcription Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
- Tumour Biology Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
- Present addresses: UMR 7216 CNRS/Epigenetics and Cell Fate, University Paris-Diderot, 35 rue Hélèn Brion, 75205 Paris cedex 13, France
- Oryzon Genomics, C/ Josep Samitier 1-5, 08028 Barcelona, Spain.
Correspondence to: Richard Treisman1 e-mail: Richard.Treisman@cancer.org.uk
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