STUDY OF THE CROSS-TALK BETWEEN THE SRC PROTO-ONCOGENE AND F-ACTIN DURING TUMOURAL TRANSFORMATION

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

Publication . 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

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.

2017-05-16Journal article

Open access