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Nat Commun. 2017 May 16;8:15237. doi: 10.1038/ncomms15237.

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

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Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, P-2780-156 Oeiras, Portugal.
Epithelial Interactions in Cancer group, Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal.
Cancer Genetics group, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (Ipatimup), Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal.
Biotechnology Center, Technische Universität Dresden, Tatzberg 47/49, 01307 Dresden, Germany.
Department of Pathology, Ipatimup Diagnostics, Ipatimup, Rua Dr Roberto Frias s/n, 4200-465 Porto, Portugal.
Ophiomics-Precision Medicine, Rua Cupertino de Miranda 9, lote 8, 1600-513 Lisboa, Portugal.
Department of Pathology, Faculty of Medicine, University of Porto, Alameda Prof. Hernaâni Monteiro, 4200-319 Porto, Portugal.


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.

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