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

2017; Nature Portfolio; Volume: 8; Issue: 1 Linguagem: Inglês

10.1038/ncomms15237

2041-1723

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

Hippo pathway signaling and YAP/TAZ

Abstract 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.