11/1/2012

Identified: New mechanism of tumoral cells reprogramation

A work published in Nature Medicine describes a new reprogrammation mechanism of the gene expression that turn into tumoral a health cell. The ICREA researcher Eduardo Eyras, head of the Regulatory Genomics Group at GRIB ( UPF-IMIM) have participated in this study.

One of the most relevant results of this study has been to establish that CPEB4 acts as a cell orchestra conductor which turns on hundreds of genes linked to tumoral growth.

The innovation is that it wouldn't be only the mutation of a concrete gene which would promote the tumor growth, but the expression in the incorrect place that "activates" hundreds of messenger molecules  (mARNs) that deliver the information contained in the genes to synthesize the proteins without these genes having been mutated.

This originates the expression of a wide variety of normal genes but in anormal amounts and moments, more typical of the first stages of the embryo's development than to  adult organs. As stated by the first authors of the study "this would be the case of tPA (Plasminogen tissular activator), a protein which is not normally found in a healthy pancreas and, nevertheless, shows high levels in pancreatic tumors.

Bioinformatics have contributed to the detection of candidate genes

In this work, Eduardo Eyras, has been responsible for the bioinformatic analysis of the Ultrasequentiation data of RNA Molecules obtained from an experiment carried out by Elena Ortiz, first author of the work, to capture RNAs which interact with CPEB4 protein.

This analysis has allowed the detection of candidate genes to be activated by CPEB4 protein in cancer and, afterwards, these genes have been experimentally verified by Pilar Navarro and Raul Mendez Groups. Among these candidate genes there was the tPA, mentioned before.

Eduardo Eyras participates together with Raul Mendez in a Consolider RNAREG project in which several Spanish labs are involved, whose main aim is the study of the role played by RNA in the regulation of cancer.

Without CEPB4 tumours reduce themselves in an 80%

An outstanding conclusion of the work is that in the studied tissues, pancreas and brain, CEPB4  is not detected in normal cells but only in tumoral ones, its inhibition would be, therefore, a very specific antitumoral treatment and with very little secondary effects, on eof the main limitations nowadays in most antitumoral therapies.

In fact, this work shows, through studies carried out in mice with tumor cells from patients, that the decrease of the CPEB4 levels in cancer cells, reduces the size of the tumors up to an 80%. Although the study is limited to two types of tumors, according to the coauthor scientists " taking into account the effects observed in the studied tumors and the type of genes regulated by this mechanism, it is expected that it participates in many other tumors.

Therefore, this work opens a new way to design new treatments against cancer. Researchers are designing and analyzing CPEB4 inhibitors with a possible thearapeutic value. Applications at a clinical level are promising although more research is needed to identify inhibitory and tested molecules before determining its clinical potential and, if applicable, be used in patients.

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