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Pere Roca-Cusachs, head of the Cellular and Molecular Mechanobiology group at IBEC (Photo: IBEC).
 30.10.2017

IBEC researchers show that physical forces activate genes involved in cancer

IBEC’s researchers at PCB, led by Pere Roca-Cusachs, reveal how forces trigger the expression of certain genes by increasing the activity of a protein called YAP in the nucleus of the cell.  The results of the study, published in Cell, have shown how these forces ‘switch on’ the expression of genes that may result in cancer.

 

Cells apply mechanical forces to their surrounding tissue, and this mechanical effect is crucial for tissue function. In diseases such as cancer or liver and lung fibrosis, tissue rigidity and mechanical forces increase, promoting the progression of the disease.

As well as playing an essential role in development by governing processes such as organ size, YAP is also known as an oncogene – in other words, it activates the transcription of genes that promote cancer by allowing cancerous cells to proliferate, or by stopping them from dying off.

The researchers saw that if a force doesn’t reach the nucleus of a cell, YAP remains in its balanced state between the cytoplasm – the cellular fluid – and the nucleus. However, if the force affects the nucleus – as occurs if there is a particularly hard area of tissue nearby, such as a tumour – the cells respond to this by opening the pores of the nucleus, allowing more YAP to enter, where it triggers the proliferation or survival genes that allow cancer to spread and grow.

“We now understand how the rigidity of tumour tissue affects cells at the gene level and promotes the survival strategy of cancerous cells,” says Pere Roca-Cusachs, head of the Cellular and Molecular Mechanobiology group at IBEC, which carried out the study together with the institute’s Cellular and Respiratory Biomechanics and Integrative Cell and Tissue Dynamics groups, in collaboration with researchers in King’s College in London.
 

More information: IBEC website [+]

Reference article: A. Elosegui-Artola, I. Andreu, A. E.M. Beedle, A. Lezamiz, M. Uroz, A. J. Kosmalska, R. Oria, J. Z. Kechagia, P. Rico-Lastres, A.-L. Le Roux, C. M. Shanahan, X. Trepat, D. Navajas, S. Garcia-Manyes and P. Roca-Cusachs (2017). “Force triggers YAP nuclear entry by regulating transport across nuclear pores“. Cell, in press. DOI: http://dx.doi.org/10.1016/j.cell.2017.10.008