4 years ago

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

Actin stress fiber organization promotes cell stiffening and proliferation of pre-invasive breast cancer cells
Maik Herbig, Sandra Tavares, José B. Pereira-Leal, Jochen Guck, André Filipe Vieira, Anna Verena Taubenberger, António Polónia, Florence Janody, Oliver Otto, Margarida Araújo, Joana Paredes, Joana Cardoso, Catarina Brás-Pereira, Nuno Pimpao Martins, Clara Barreto
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.

Publisher URL: http://www.nature.com/articles/ncomms15237

DOI: 10.1038/ncomms15237

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