The researchers demonstrated that FMRP acts as a master switch controlling the levels of several proteins involved in different stages of aggressive breast cancer, including the invasion of cancer cells into blood vessels and the spread of these cancer cells to other tissues forming metastasis. The work is published on-line in EMBO Molecular Medicine.
Claudia Bagni: “Breast cancer is the most common form of cancer in women. It often comes back years after treatment and spreads throughout the body. We here show a correlation between the FMRP level in breast tissue and the chance of the spread of cancer to other organs. I hope that we can use this knowledge to develop a test to predict the likelihood of metastasis.”
The authors identified high levels of FMRP in human breast cancer tissue microarrays and also examined the effects of FMRP levels in a mouse model to study breast cancer. In these mice, high levels of FMRP in primary breast cancer tumors were also linked to the spread of the cancer to the lungs and the development of metastasis. Importantly, reduction of FMRP, on the contrary lead to a decrease of metastasis formation and protection against breast cancer in individuals lacking this protein.
The role of FMRP is well known in the brain, where its absence leads to Fragile X Syn-drome, the most prevalent form of inherited intellectual disability in humans. The present study explored the direct relationship between the levels of FMRP and the progression of breast cancer.
“Previous studies indicated that patients with Fragile X Syndrome had a decreased risk of developing cancer but little is known about the molecular events that lead to this beneficial effect. We showed that high levels of the FMRP protein in human breast tissue samples are linked to increased risk of breast cancer and the spread of the disease to other tissues throughout the body,” EMBO Member Claudia Bagni from VIB/KU Leuven, Belgium/ University of Rome Tor Vergata, Italy, who led the study, remarked. “Our results suggest that FMRP acts as a master regulator of a large group of mRNAs that are involved in multiple steps of cancer progression”.
The researchers suggest that the levels of FMRP might be used as an indicator of aggressive breast cancer and could be used to predict the likelihood of the spread of cancer to other organs like the lung. In fact, the authors found that FMRP levels correlate with the highly aggressive Triple Negative Breast Cancer. Breast cancer is the most common form of cancer in women and has a poor prognosis. It often comes back years after treatment and spreads throughout the body.
“The Fragile X Protein binds mRNAs involved in cancer progression and
modulates metastasis formation”
Rossella Luca, 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
EMBO Molecular Medicine, 2013
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