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XBP1 may be a key element for the prevention of the development of liver cancer

Researchers at CIMA describe that XBP1 could be a key agent in avoiding the accumulation of mutations

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Jesús Prieto, Josepmaría Argemí, Tomás Aragón and Roberto Ferrero, at CIMA of the University of Navarra. FOTO: Manuel Castells
05/04/17 12:05 María Pilar Huarte

The liver is the only organ in the human body capable of regeneration after a surgical resection. To date, the cell mechanisms that come into play in its regenerative capacity are unknown, therefore, as yet, there is no treatment that improves it in patients who have had an extensive liver resection.

In the most recent issue of Gastroenterology, a prestigious scientific journal in the area of gastrointestinal and liver diseases, researchers at the Center for Applied Medical Research (CIMA) of the University of Navarra describe a protein which protects DNA during hepatic regeneration in mice. “It was known that XBP1 is a response protein in situations of metabolic demand, but in our work we have found that this protein, moreover, regulates numerous functions during the regeneration. Outstanding amongst these is its capacity to protect DNA from the damage it may suffer during the cell multiplication that occurs in the liver during regeneration”, explained Dr. Tomás Aragón and Dr. Jesús Prieto, co-directors of the work. The CIMA researchers have confirmed that mice without XBP1 in the liver have a higher number of DNA breaks and, consequently, the organ cannot regenerate normally after a partial resection. Dr. Josepmaria Argemí, lead author of the work, believes that this new function of XBP1 "may result in the conception of new treatments to promote a regeneration of the remaining liver in a more effective and healthy way”. 

Pie de figura: Tras una operación en la que se elimina una sección del hígado se establece una situación inflamatoria mediada por la citoquina IL6 que activa la expresión de la proteína XBPI. Esta proteína viaja al núcleo de las células hepáticas (los hepatocitos) y promueve la expresión de genes para responder a la fase inflamatoria, facilitar el plegamiento de proteínas y reparar el daño al genoma. Así, en hígados donde los niveles de XBP1 son menores, se acumula el daño al ADN, evidenciado por la activación de la proteína gamma H2Ax.

A key agent against hepatic cancer

The results obtained in the work contribute to improving knowledge regarding DNA protection in liver cells. Thus, as the researchers point out, "XBP1 could be a key agent in avoiding the accumulation of mutations that tends to lead to the development of cancer in different tissues”. “Although there is still a long way to go, we believe that in a not very distant future we shall learn whether XBP1 is a new piece in the complex jigsaw puzzle of mechanisms that prevent the emergence of a cancer”, they conclude.

The work, which has involved a functional analysis of the entire genome, was carried out in collaboration with Dr. Bruno Amati and Dr. Theresia Kress, from the Istituto Europeo di Oncologia in Milan (Italy). It has been funded by the European Union, the Ministry for Science and Innovation and that of Economy and Competitiveness in Spain, the Ministry for Health in Italy, the Italian Association for Research into Cancer and the MTorres Foundation.

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