IRB Barcelona discovers a mechanism that accelerates tumor development

By Biocat

Nature has published a paper by the lab headed by Dr. Raúl Méndez, ICREA professor at the Institute for Research in Biomedicine (IRB Barcelona). The study describes a mechanism controlled by the CPEB1 protein that affects more than 200 genes related to cell proliferation and tumor progression.

Raúl Méndez is an expert on the CPBE protein family, a type of RNA-binding protein that has a positive and crucial role in early embryo development. “CPEB proteins are necessary during development and also during tissue regeneration via stem cells in adults, but if the programme governed by CPEBs is continually switched on, cells divide when they are not supposed to and form a tumor”, explains Méndez.

The CPEB family comprises four proteins, which compensate each other’s normal function but which have specific activities in diseased states. “This finding is positive from a therapeutic viewpoint because it means that if you remove CPEB1 from healthy cells, its function can be taken over by any other CPEB protein. In contrast, in tumors only CPEB1 has the capacity to shorten these regions, thus affecting only tumor cells”, states Italian researcher Felice Alessio Bava, first author of the paper, and post-doctoral fellow with Méndez’s group who, this year, has obtained his doctorate degree through the “la Caixa” International Fellowship Programme.

This study provides further evidence of the potential of CPEB proteins as therapeutic targets. In 2011, Méndez identified that CPEB4 “switches on” hundreds of genes linked to tumor growth. This new study explains that the overexpression of CPEB4 in tumors is because CPEB1 has also “released its brakes”.

The lab has developed a system to screen therapeutic molecules for a drug that can inhibit the action of CPEB in tumors while having few secondary effects on healthy cells. “There is no drug currently available that influences the regulation of gene expression at this level. Our findings open up a pioneering therapeutic window. We are optimistic about the potential of CPEB proteins as targets”, says Méndez.

The study has involved the collaboration of the group led by Juan Valcárcel at the Center for Genomic Regulation (CRG), an expert in RNA nuclear processing, and that of Roderic Guigó, an expert in biostatistics and also at CRG. This study received funding from the Consolider RNAreg consortium of the Spanish Ministry of Economy and Competition and the Government of Catalonia.

Mor information is available in the IRB Barcelona website.

Reference article: CPEB1 coordinates alternative 3'UTR formation with translational regulation. Felice-Alessio Bava, Carolina Eliscovich, Pedro G. Ferreira, Belen Miñana, Claudia Ben-Dov, Roderic Guigó, Juan Valcárcel and Raúl Méndez. Nature (2013) doi: 10.1038/nature11901