Actin stress fiber organization promotes cell stiffening and proliferation of pre-invasive breast cancer cells

Tavares, Sandra; Vieira, André Filipe; Taubenberger, Anna Verena; Araújo, Margarida; Martins, Nuno Pimpao; Brás-Pereira, Catarina; Polónia, António; Herbig, Maik; Barreto, Clara; Otto, Oliver; Cardoso, Joana; Pereira-Leal, José B.; Guck, Jochen; Paredes, Joana; Janody, Florence

http://hdl.handle.net/10400.7/756

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Authors

Tavares, Sandra

Vieira, André Filipe

Taubenberger, Anna Verena

Araújo, Margarida

Martins, Nuno Pimpao

Brás-Pereira, Catarina

Abstract(s)

Studies of the role of actin in tumour progression have highlighted its key contribution in cell softening associated with cell invasion. Here, using a human breast cell line with conditional Src induction, we demonstrate that cells undergo a stiffening state prior to acquiring malignant features. This state is characterized by the transient accumulation of stress fibres and upregulation of Ena/VASP-like (EVL). EVL, in turn, organizes stress fibres leading to transient cell stiffening, ERK-dependent cell proliferation, as well as enhancement of Src activation and progression towards a fully transformed state. Accordingly, EVL accumulates predominantly in premalignant breast lesions and is required for Src-induced epithelial overgrowth in Drosophila. While cell softening allows for cancer cell invasion, our work reveals that stress fibre-mediated cell stiffening could drive tumour growth during premalignant stages. A careful consideration of the mechanical properties of tumour cells could therefore offer new avenues of exploration when designing cancer-targeting therapies.

Description

This deposit is composed by the main article and supplementary files of the publication.

Keywords

Biophysics Cancer Cytoskeleton

URI

http://hdl.handle.net/10400.7/756

Citation

Tavares, S. et al. Actin stress fiber organization promotes cell stiffening and proliferation of pre-invasive breast cancer cells. Nat. Commun. 8, 15237 doi: 10.1038/ncomms15237 (2017).