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Pere Roca-Cusachs (Photo: IBEC).

A study led by IBEC reveals a key mechanism to slow the progression of breast tumors

A study led by Pere Roca-Cusachs, principal investigator at the Institute for Bioengineering of Catalonia (IBEC), based in the Barcelona Science Park, demonstrates that laminin, a protein present in breast tissues, prevents the effects of stiffening, protecting cells against tumor growth. The results of the work, published today in Nature Materials, is part of the European project Mechano·Control, receiving funding exceeding 7 million euros within the framework of the European FET (Future and Emerging Technologies) projects.

Cells are capable of translating mechanical changes into biological responses. This process is known as mechanotransduction and plays a fundamental role in the progression of solid tumors, such as breast cancer.

It is well-established that a common mechanical alteration in cancer progression involves tissue hardening. This stiffness is precisely what is detected during self-examinations or breast palpations for potential tumor detection. The stiffness of breast tissue triggers a chain reaction, inducing tension within cells and distorting their nuclei. Ultimately, this nuclear deformation activates genes responsible for controlling cell proliferation, which are closely associated with tumor growth.

The results of the study led by Pere Roca-Cusachs -principal investigator at IBEC and Serra-Hunter associate professor at the University of Barcelona (UB)- indicates that laminin, a protein that provides structure and support to breast tissues, hinders the mechanotransduction process in cells, thereby protecting the nucleus from deformation.

“Our findings demonstrate that the presence of laminin mitigates the effects of stiffness, effectively shielding cells from tumor growth. We have showcased this mechanism in vitro, but we believe it holds potential for in vivo application, considering what we have observed in samples from breast cancer patients”, explains Zanetta Kechagia, postdoctoral researcher at IBEC and first author of the study.

“Through this mechanism, which we have shown can prevent the invasion of tumor cells, there is potential for the development of more sensitive diagnostic tools or even new therapies for breast cancer. However, further research will be needed to explore these possibilities”, reveals Roca-Cusachs.

This work is part of the European project Mechano·Control, receiving funding exceeding 7 million euros within the framework of the European FET (Future and Emerging Technologies) projects.

This research also includes significant contributions of researchers from other institutions participating in this consortium, such as Pablo Sáez and Marino Arroyo from Universitat Politècnica de Catalunya, and Thijs Koorman and Patrick Derksen from University Medical Center Utrecht, The Netherlands.

“These results represent the culmination of over 6 years of work, during which we received support from the European Commission and collaborated with a team of international institutions, led by IBEC, to better understand how mechanical forces impact breast cancer,” says Daniel Caudepón, IBEC project manager overseeing Mechano-Control.

» Referenced article: Zanetta Kechagia, Pablo Sáez, Manuel Gómez-González, Brenda Canales, Srivatsava Viswanadha, Martín Zamarbide, Ion Andreu, Thijs Koorman, Amy E. M. Beedle, Alberto Elosegui-Artola, Patrick W. B. Derksen, Xavier Trepat, Marino Arroyo & Pere Roca-Cusachs. “The laminin–keratin link shields the nucleus from mechanical deformation and signalling”. Nature Materials (2023). DOI: 10.1038/s41563-023-01657-3.

» For further information: IBEC website [+]