A group of researchers of the University of Oviedo led by professor of Biochemistry and Molecular Biology Carlos López-Otín, in collaboration with the Universiy Central Hospital of Asturias, the University of Cambridge, the National Center for Cardiovascular Research and the Institutes for Biomedical Research of Bellvitge and 12 de Octubre Hospital, ha identificado un nuevo supresor tumoral hematológico, la protein AIRAPL. These findings, published today in the journal Nature Medicine, have allowed them to suggest a new treatment for the síndromes related to myeloproliferative neoplasms, frequent in older people.

Researchers have focused their study on the protein AIRAPL, whose biological function was completely unknown so far. In order to carry out this work, they produced genetically modified mice, which lacked the gene that codified this protein. "Mice that lacked AIRAPL developed myeloproliferative syndromes, which proves the tumor suppression function of AIRAPL in these hematological diseases", highlights Carlos López-Otín. Researchers were also able to verify that this protein expression is suppressed in the bone marrow of patients suffering from myeloproliferative neoplasms.

The study proves that it is possible to generate tumors through changes that affect protein stability without accumulating mutations in the genome

The detailed analysis of biological disorders caused by the lack of AIRAPL, allowed experts to prove that AIRAPL regulates the molecular route of the growth factor IGF-1, involved in both tumoral processes and aging. "AIRAPL controls the levels of IGF-1 receptor, thus conditioning the activity of this route. The lack of AIRAPL, IGF-1 signaling is uncommonly active, which causes myeloproliferative disorders", highlights José María Pérez Freije, co-director of the work.

The identification of this mechanism opens new pathways for the treatment of this pathology. Therefore, researchers have proved that inhibition of IGF-1 factor reverts hematological disorders in mice lacking AIRAPL. "Our work has made it possible to identify new diagnostic markers and therapeutic targets in these syndromes", says Fernando G. Osorio.

This project has as a previous background in other works developed by this research group and published in Nature, Nature Medicine, Cell and Science Translational Medicine, in which they described molecular disorders, involved in different tumors and accelerated aging syndromes. "This work provides keys on the relationship between aging processes and cancer in the hematological system and at the same time disseminates the idea that changes in routes like IGF-1, are essential in both processes. Moreover, our study shows that it is possible to generate new tumors just by altering the proteins stability, without having cells accumulating mutations in their genome", explains López-Otín

Reference

• Referencia Loss of the proteostasis factor AIRAPL causes myeloid transformation by deregulating IGF-1 signaling. Nature Medicine.
• Researchers involved in this project: Fernando G. Osorio, Clara Soria-Valles, Olaya Santiago-Fernández, Teresa Bernal, María Mittelbrunn, Enrique Colado, Francisco Rodríguez, Elena Bonzon-Kulichenko, Jesús Vázquez, Montserrat Porta-de-la-Riva, Julián Cerón, Antonio Fueyo, Juan Li, Anthony R Green, José M.P. Freije and Carlos López-Otín.