Researchers establish how tissue stiffness activates cancer
Researchers at Institute for Bioengineering of Catalonia (IBEC) and University of Barcelona, headed by Pere Roca-Cusachs, teacher at the Faculty of Medicine, have discovered the way tissue stiffness activates cancer. This new founding helps to come up with new strategies to stop or reduce the growth of the tumor.
Researchers at Institute for Bioengineering of Catalonia (IBEC) and University of Barcelona, headed by Pere Roca-Cusachs, teacher at the Faculty of Medicine, have discovered the way tissue stiffness activates cancer. This new founding helps to come up with new strategies to stop or reduce the growth of the tumor.
The results, born from the collaboration between researchers at IBEC and the Georgia Institute of Technology, have been published in Nature Cell Biology —where they identify how the tissue stiffness mechanism activates an oncogene called YAP, and how it has to be stopped.
This discovery is the result of a long time work researching the forces that cells apply to their surrounding tissue. These forces determine how cells proliferate, differentiate and move. They also regulate the development, the tumorigenesis and wound healing.
“This result is relevant because most of the solid tumors are more rigid than the normal tissue, for example, hard lumps can be a breast cancer symptom”, says Roca-Cusachs -“But now we can go further; increasing or decreasing tissue stiffness can reinforce or weaken the tumor progression”.
“Cells have to use the forces of their surrounding tissue in order to detect its stiffness, just as a person would need to sit on a mattress to know about its softness”, says Alberto Elósegui-Artola, researcher at IBEC and author of the article- “This is done through molecules like the integrins, which bind cells to the surrounding extracellular matrix, and the talin, which connects integrins to the cytoskeleton or body of the cell”.
Researchers have discovered that, if the tissue is stiff, the forces cells use to pull from these molecules can unfold the talin. When this happens, the protein exposes a binding area to another protein named vinculin- which binds and eases the activation of YAP- an important factor in the tumor progression. However, is the tissue is soft, the force goes slow. This breaks the union between integrin and tissue before the talin is unfolded, and it stops the activation of the YAP. According to the researchers, this is an important first step towards the possibility of creating a medicine or strategy based on this principle, which could stop the growth of many types of cancer such as breast cancer, lung cancer, prostate, skin and many others.
This study was funded in part by the Marató de Tv3.
Reference:
A. Elosegui Artola, R. Oria, Y. Chen, A. Kosmalska, C. Pérez González, N. Castro, Ch. Zhu, X. Trepat, P. Roca Cusachs. “Mechanical regulation of a molecular clutch defines force transmission and transduction in response to matrix rigidity”. Nature Cell Biology, abril de 2016. DOI: 10.1038/ncb3336