FMRP PROTEIN RESPONSIBLE FOR FRAGILE X SYNDROME INTELLECTUAL DISABILITY ALSO INVOLVED IN BREAST CANCER PROGRESSION

“The fragile X protein binds mRNAs involved in cancer progression and modulates metastasis formation”:
Rossella Lucá, Michele Averna, Francesca Zalfa, Manuela Vecchi, Fabrizio Bianchi, Giorgio La Fata, Franca del Nonno, Roberta Nardacci, Marco Bianchi, Paolo Nuciforo, Sebastian Munck, Paola Parrella, Rute Moura, Emanuela Signori, Robert Alston, Anna Kuchnio, Maria Giulia Farace, Vito Michele Fazio, Mauro Piacentini, Bart De Strooper, Tilmann Achsel, Giovanni Neri, Patrick Neven, D. Gareth Evans, Peter Carmeliet, Massimiliano Mazzone, and Claudia Bagni
 
More information on the EMBO Molecular Medicine journal is available at:
www.embomolmed.org
 
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Prof. Claudia Bagni
Department of Biomedicine and Prevention
University of Rome “Tor Vergata”
Ph. (Italy): +39 347 464 6896
Ph. (Belgium): +32 499 459 167
A research group led by Prof. Claudia Bagni of the Department of Biomedicine and Prevention at the University of Rome “Tor Vergata”, in collaboration with the VIB/University of Leuven, Belgium, has discovered the way in which the fragile X syndrome protein (FMRP) contributes to the progression of breast cancer. In accomplishing this objective, Prof. Bagni’s team also worked with various research centers and hospitals in Italy (including the IFOM-IEO Campus in Milan and the Campus Bio-Medico University of Rome) as well as abroad (both in Belgium and the United Kingdom). The researchers have demonstrated that FMRP acts as a molecular “switch” that is capable of controlling the levels of other proteins involved in different stages of the progression of breast cancer, such as the spread of cancer cells in the bloodstream and the invasion of other organs to form metastases. The study has been published online in the international scientific journal EMBO Molecular Medicine.
 
“Breast cancer is the most common form of cancer in women. This type of cancer can recur even many years after treatment, giving rise to metastases which spread throughout the body. We have shown that there is a close link between the levels of the FMRP protein in tumor tissue and the ability of cancer cells to spread to other organs. I hope that our discovery can pave the way for the development of new tests to predict the likelihood of metastasization in breast cancer”, stated Prof. Bagni of the University of Rome “Tor Vergata” and the VIB/University of Leuven.
The researchers found very high levels of FMRP in a large percentage of highly-invasive breast tumors (using the tissue microarray approach) and also examined the effect on cancer cells of modulation of FMRP levels, using a mouse model to study breast cancer. In this mouse model, an increase in FMRP levels in the primary tumor led to a rapid and massive spread of cancer cells in the bloodstream and to the development of metastases in the lungs. In contrast, a reduction in levels of the protein led to a decrease in the formation of metastases in the lungs. Another interesting point is that people with fragile X syndrome, who lack the FMRP protein, have a reduced risk of developing breast cancer, as well as an unusual protection against the invasiveness and aggressiveness of this and of other forms of cancer.
There have been extensive studies done on the role played by FMRP in the brain, where the absence of this protein leads to fragile X syndrome, the most common form of inherited intellectual disability in humans. However, this study explored for the first time the direct relationship that exists between FMRP levels and the progression of breast cancer.
“Previous studies indicated that patients with fragile X syndrome had a lower risk of developing cancer, but little is still known about the molecular events that give rise to this beneficial effect. We have shown that high levels of the FMRP protein in human breast tissue samples are linked to an increased risk of developing cancer and particularly to a higher risk of the spread of cancer cells to other tissues in the body”, underlined Prof. Claudia Bagni, who headed the study. “Our results suggest that FMRP can act as a master regulator of a large group of molecules involved in various stages of breast cancer progression. We hope that FMRP levels can be used in the future as an indicator of aggressiveness in breast cancer in order to predict the likelihood of metastatic spread to other organs like the lungs”.