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

作者：Tavares Sandra; Vieira Andre Filipe; Taubenberger Anna Verena; Araujo Margarida; Martins Nuno Pimpao; Bras Pereira Catarina; Polonia Antonio; Herbig Maik; Barreto Clara; Otto Oliver; Cardoso Joana; Pereira Leal Jose B; Guck Jochen; Paredes Joana; Janody Florence^*

来源：Nature Communications, 2017, 8(1): 15237.

DOI：10.1038/ncomms15237

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.

• 出版日期2017-5-16