Imperial College London

ProfessorLucaMagnani

Faculty of MedicineDepartment of Surgery & Cancer

Chair in Cancer Adaptation and Evolution
 
 
 
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Contact

 

+44 (0)20 7594 2808l.magnani CV

 
 
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Location

 

137ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Perone:2018:10.1101/380634,
author = {Perone, Y and Farrugia, AJ and Meira, AR and Gyrffy, B and Ion, C and Uggetti, A and Patten, D and Chronopoulos, A and Faronato, M and Shousha, S and Steel, JH and Davies, C and Patel, N and Rio, Hernandez AD and Coombes, C and Pruneri, G and Lim, A and Calvo, F and Magnani, L},
doi = {10.1101/380634},
title = {SREBP1 drives KRT80-dependent cytoskeletal changes and invasive behavior in endocrine resistant ERα breast cancer},
url = {http://dx.doi.org/10.1101/380634},
year = {2018}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - <jats:title>Abstract</jats:title><jats:p>Approximately 30% of women diagnosed with ERα breast cancer relapse with metastatic disease following adjuvant treatment with endocrine therapies<jats:sup>1,2</jats:sup>. The connection between acquisition of drug resistance and invasive potential is poorly understood. In this study, we demonstrate that the type II keratin topological associating domain (TAD)<jats:sup>3</jats:sup> undergoes epigenetic reprogramming in cells that develop resistance to aromatase inhibitors (AI), leading to keratin 80 (KRT80) upregulation. In agreement, an increased number of KRT80-positive cells are observed at relapse <jats:italic>in vivo</jats:italic> while KRT80 expression associates with poor outcome using several clinical endpoints. KRT80 expression is driven by <jats:italic>de novo</jats:italic> enhancer activation by sterol regulatory element-binding protein 1<jats:sup>4</jats:sup> (SREBP1). KRT80 upregulation directly promotes cytoskeletal rearrangements at the leading edge, increased focal adhesion maturation and cellular stiffening, which collectively promote cancer cell invasion. Shear-wave elasticity imaging of prospective patients shows that KRT80 levels correlate with stiffer tumors <jats:italic>in vivo</jats:italic>. Collectively, our data uncover an unpredicted and potentially targetable direct link between epigenetic and cytoskeletal reprogramming promoting cell invasion in response to chronic AI treatment.</jats:p>
AU - Perone,Y
AU - Farrugia,AJ
AU - Meira,AR
AU - Gyrffy,B
AU - Ion,C
AU - Uggetti,A
AU - Patten,D
AU - Chronopoulos,A
AU - Faronato,M
AU - Shousha,S
AU - Steel,JH
AU - Davies,C
AU - Patel,N
AU - Rio,Hernandez AD
AU - Coombes,C
AU - Pruneri,G
AU - Lim,A
AU - Calvo,F
AU - Magnani,L
DO - 10.1101/380634
PY - 2018///
TI - SREBP1 drives KRT80-dependent cytoskeletal changes and invasive behavior in endocrine resistant ERα breast cancer
UR - http://dx.doi.org/10.1101/380634
ER -