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A study conducted by the UB describes cell mechanisms in planarians through which the Hippo pathway creates tumors

Researchers from the Department of Genetics, Microbiology and Statistics of the University of Barcelona and the Institute of Biomedicine of the University of Barcelona (IBUB) have described the mechanisms through which the intercellular signalling pathway Hippo, is involved in the tumor development.

Researchers from the Department of Genetics, Microbiology and Statistics of the University of Barcelona and the Institute of Biomedicine of the University of Barcelona (IBUB) have described the mechanisms through which the intercellular signalling pathway Hippo, is involved in the tumor development.

The results of the new study prove blocking the Hippo pathway in planarians does not result in bigger worms but instead it causes tumors directly.

The results of the new study prove blocking the Hippo pathway in planarians does not result in bigger worms but instead it causes tumors directly.

28/02/2018

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Researchers from the Department of Genetics, Microbiology and Statistics of the University of Barcelona and the Institute of Biomedicine of the University of Barcelona (IBUB) have described the mechanisms through which the intercellular signalling pathway Hippo, is involved in the tumor development. The study, led by Teresa Adell, lecturer from the mentioned Department of the UB, found that this chain of biochemical reactions controls the cell cycle and limits the cell plasticity in planarians, a type of flatworm which can regenerate any part of its body. These results, shown in the cover of the journal PLOS Biology , favour the understanding of the Hippo path, and the tumoral processes, since it shows that the cell base of the tumor creation is not based on an increase of cell proliferation but in the malfunctioning of other processes that cause cells to act in an uncontrolled way.

 

Other participants of the study are the UB experts Jose Ignacio Rojo-Laguna, Emili Saló and Nídia de Sousa, first signer of the article, and Gustavo Rodríguez-Esteban, researcher from the National Centre for Genome Analysis (CNAG).

 

Worms that can regenerate any part of their body

Planarians are freshwater worms that became a key model for the study of cell renewal, since they can regenerate any part of their body, even their heads, in two weeks. This surprising plasticity is based on the presence of a population of totipotent adult stem cells (neoblasts), able to form any kind of cell in the body.

The aim of the study was to analyse the Hippo path (hippopotamus-like phenotype) in this model organism. The Hippo pathway is a communication mechanism among cells, and when inhibited, like in the case of the vinegar fly or in mice, it produces larger organs, hence its name. Therefore, they thought this pathway was controlling cell proliferation and the size of organs. However, it has been proved that the pathway’s inhibition caused tumors.

 

Hippo pathway controls cell differentiation

The results of the new study prove blocking the Hippo pathway in planarians does not result in bigger worms, which would be the expected result according to what happens in other animal models like the vinegar fly, but instead it causes tumors directly. The molecular study of these planarians enabled researchers to deduce the Hippo pathway does not control cell proliferation but other essential processes such as cell death, the cell cycle and the maintenance of the differentiated state of cells.

“Differentiated cells have a clear function within the organism (skin cells, neurons, etc.) and they cannot proliferate. Instead, if there is no hippo, these cells can go back and become totipotent cells again, able to turn into any kind of cell and proliferate”, says Teresa Adell. “If you join this ability which, without the hippo pathway, cell death is also inhibited , this is a ‘bomb’: you have cells that differentiated wrongly, they can have daughters that are not normal, and they cannot die, so inevitably wrong cells are accumulated in the genetic material, and these is the origin of tumors”, notes the researcher.

 

Implication with human tumors

These results have a big importance to understand human tumor processes, since these are essential cell mechanisms which are kept over evolution and which explain the development process in animals and humans. According to the researchers, the inhibition of the hippo pathway is not the direct cause of tumors, but it is necessary for their progress. “Knowinng more about the functioning of the pathway allows us to point up the way of the tumor progress. The pathway inhibition does not cause tumors in humans directly, but it is necessary for them to progress, and therefore, we can conclude that promoting the undifferentiated state and not proliferation, is a pre-requirement for the tumor to progress”, concludes the researcher.

 

Article reference:

de Sousa, N., Rodríguez-Esteban, G., Rojjo-Laguna, J.I., Saló E. and Adell T.. “Hipposignaling controls cell cycleandrestricts cell plasticity in planarians”. PLOS Biology . January 2018. Doi: https://doi.org/10.1371/journal.pbio.2002399

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