Abstract
The role of the fragile X mental retardation protein (FMRP) is well established in brain, where its absence leads to the fragile X syndrome (FXS). FMRP is almost ubiquitously expressed, suggesting that, in addition to its effects in brain, it may have fundamental roles in other organs. There is evidence that FMRP expression can be linked to cancer. FMR1 mRNA, encoding FMRP, is overexpressed in hepatocellular carcinoma cells. A decreased risk of cancer has been reported in patients with FXS while a patient-case with FXS showed an unusual decrease of tumour brain invasiveness. However, a role for FMRP in regulating cancer biology, if any, remains unknown. We show here that FMRP and FMR1 mRNA levels correlate with prognostic indicators of aggressive breast cancer, lung metastases probability and triple negative breast cancer (TNBC). We establish that FMRP overexpression in murine breast primary tumours enhances lung metastasis while its reduction has the opposite effect regulating cell spreading and invasion. FMRP binds mRNAs involved in epithelial mesenchymal transition (EMT) and invasion including E-cadherin and Vimentin mRNAs, hallmarks of EMT and cancer progression.
| Original language | English |
|---|---|
| Pages (from-to) | 1523-1536 |
| Number of pages | 14 |
| Journal | EMBO Molecular Medicine |
| Volume | 5 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 2013 |
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Keywords
- Cell invasion
- EMT
- FMRP
- MRNA metabolism
- TNBC
ASJC Scopus subject areas
- Molecular Medicine
Cite this
The Fragile X Protein binds mRNAs involved in cancer progression and modulates metastasis formation. / Lucá, Rossella; Averna, Michele; Zalfa, Francesca; Vecchi, Manuela; Bianchi, Fabrizio; Fata, Giorgio La; Del Nonno, Franca; Nardacci, Roberta; Bianchi, Marco; Nuciforo, Paolo; Munck, Sebastian; Parrella, Paola; Moura, Rute; Signori, Emanuela; Alston, Robert; Kuchnio, Anna; Farace, Maria Giulia; Fazio, Vito Michele; Piacentini, Mauro; De Strooper, Bart; Achsel, Tilmann; Neri, Giovanni; Neven, Patrick; Evans, D. Gareth; Carmeliet, Peter; Mazzone, Massimiliano; Bagni, Claudia.
In: EMBO Molecular Medicine, Vol. 5, No. 10, 10.2013, p. 1523-1536.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The Fragile X Protein binds mRNAs involved in cancer progression and modulates metastasis formation
AU - Lucá, Rossella
AU - Averna, Michele
AU - Zalfa, Francesca
AU - Vecchi, Manuela
AU - Bianchi, Fabrizio
AU - Fata, Giorgio La
AU - Del Nonno, Franca
AU - Nardacci, Roberta
AU - Bianchi, Marco
AU - Nuciforo, Paolo
AU - Munck, Sebastian
AU - Parrella, Paola
AU - Moura, Rute
AU - Signori, Emanuela
AU - Alston, Robert
AU - Kuchnio, Anna
AU - Farace, Maria Giulia
AU - Fazio, Vito Michele
AU - Piacentini, Mauro
AU - De Strooper, Bart
AU - Achsel, Tilmann
AU - Neri, Giovanni
AU - Neven, Patrick
AU - Evans, D. Gareth
AU - Carmeliet, Peter
AU - Mazzone, Massimiliano
AU - Bagni, Claudia
PY - 2013/10
Y1 - 2013/10
N2 - The role of the fragile X mental retardation protein (FMRP) is well established in brain, where its absence leads to the fragile X syndrome (FXS). FMRP is almost ubiquitously expressed, suggesting that, in addition to its effects in brain, it may have fundamental roles in other organs. There is evidence that FMRP expression can be linked to cancer. FMR1 mRNA, encoding FMRP, is overexpressed in hepatocellular carcinoma cells. A decreased risk of cancer has been reported in patients with FXS while a patient-case with FXS showed an unusual decrease of tumour brain invasiveness. However, a role for FMRP in regulating cancer biology, if any, remains unknown. We show here that FMRP and FMR1 mRNA levels correlate with prognostic indicators of aggressive breast cancer, lung metastases probability and triple negative breast cancer (TNBC). We establish that FMRP overexpression in murine breast primary tumours enhances lung metastasis while its reduction has the opposite effect regulating cell spreading and invasion. FMRP binds mRNAs involved in epithelial mesenchymal transition (EMT) and invasion including E-cadherin and Vimentin mRNAs, hallmarks of EMT and cancer progression.
AB - The role of the fragile X mental retardation protein (FMRP) is well established in brain, where its absence leads to the fragile X syndrome (FXS). FMRP is almost ubiquitously expressed, suggesting that, in addition to its effects in brain, it may have fundamental roles in other organs. There is evidence that FMRP expression can be linked to cancer. FMR1 mRNA, encoding FMRP, is overexpressed in hepatocellular carcinoma cells. A decreased risk of cancer has been reported in patients with FXS while a patient-case with FXS showed an unusual decrease of tumour brain invasiveness. However, a role for FMRP in regulating cancer biology, if any, remains unknown. We show here that FMRP and FMR1 mRNA levels correlate with prognostic indicators of aggressive breast cancer, lung metastases probability and triple negative breast cancer (TNBC). We establish that FMRP overexpression in murine breast primary tumours enhances lung metastasis while its reduction has the opposite effect regulating cell spreading and invasion. FMRP binds mRNAs involved in epithelial mesenchymal transition (EMT) and invasion including E-cadherin and Vimentin mRNAs, hallmarks of EMT and cancer progression.
KW - Cell invasion
KW - EMT
KW - FMRP
KW - MRNA metabolism
KW - TNBC
UR - http://www.scopus.com/inward/record.url?scp=84884926024&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884926024&partnerID=8YFLogxK
U2 - 10.1002/emmm.201302847
DO - 10.1002/emmm.201302847
M3 - Article
C2 - 24092663
AN - SCOPUS:84884926024
VL - 5
SP - 1523
EP - 1536
JO - EMBO Molecular Medicine
JF - EMBO Molecular Medicine
SN - 1757-4676
IS - 10
ER -