Imperial College London

DrSilviaOttaviani

Faculty of MedicineDepartment of Surgery & Cancer

Honorary Lecturer
 
 
 
//

Contact

 

+44 (0)20 7594 2823silvia.ottaviani

 
 
//

Location

 

ICTEM buildingHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Pellegrino:2013:nar/gkt245,
author = {Pellegrino, L and Stebbing, J and Braga, VM and Frampton, AE and Jacob, J and Buluwela, L and Jiao, LR and Periyasamy, M and Madsen, CD and Caley, MP and Ottaviani, S and Roca-Alonso, L and El-Bahrawy, M and Coombes, RC and Krell, J and Castellano, L},
doi = {nar/gkt245},
journal = {Nucleic Acids Research},
pages = {5400--5412},
title = {miR-23b regulates cytoskeletal remodeling, motility and metastasis by directly targeting multiple transcripts},
url = {http://dx.doi.org/10.1093/nar/gkt245},
volume = {41},
year = {2013}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Uncontrolled cell proliferation and cytoskeletal remodeling are responsible for tumor development and ultimately metastasis. A number of studies have implicated microRNAs in the regulation of cancer cell invasion and migration. Here, we show that miR-23b regulates focal adhesion, cell spreading, cell-cell junctions and the formation of lamellipodia in breast cancer (BC), implicating a central role for it in cytoskeletal dynamics. Inhibition of miR-23b, using a specific sponge construct, leads to an increase of cell migration and metastatic spread in vivo, indicating it as a metastatic suppressor microRNA. Clinically, low miR-23b expression correlates with the development of metastases in BC patients. Mechanistically, miR-23b is able to directly inhibit a number of genes implicated in cytoskeletal remodeling in BC cells. Through intracellular signal transduction, growth factors activate the transcription factor AP-1, and we show that this in turn reduces miR-23b levels by direct binding to its promoter, releasing the pro-invasive genes from translational inhibition. In aggregate, miR-23b expression invokes a sophisticated interaction network that co-ordinates a wide range of cellular responses required to alter the cytoskeleton during cancer cell motility.
AU - Pellegrino,L
AU - Stebbing,J
AU - Braga,VM
AU - Frampton,AE
AU - Jacob,J
AU - Buluwela,L
AU - Jiao,LR
AU - Periyasamy,M
AU - Madsen,CD
AU - Caley,MP
AU - Ottaviani,S
AU - Roca-Alonso,L
AU - El-Bahrawy,M
AU - Coombes,RC
AU - Krell,J
AU - Castellano,L
DO - nar/gkt245
EP - 5412
PY - 2013///
SN - 1362-4962
SP - 5400
TI - miR-23b regulates cytoskeletal remodeling, motility and metastasis by directly targeting multiple transcripts
T2 - Nucleic Acids Research
UR - http://dx.doi.org/10.1093/nar/gkt245
UR - http://hdl.handle.net/10044/1/34177
VL - 41
ER -