Imperial College London


Faculty of MedicineDepartment of Surgery & Cancer

Professor of Molecular Endocrine Oncology



+44 (0)20 7594 2811simak.ali




133ICTEM buildingHammersmith Campus






BibTex format

author = {Yague, E and Asaduzzaman, M and Constantinou, S and Haoxiang, M and Gallon, J and Lin, ML and Singh, P and Raguz, S and Ali, S and Shousha, S and Coombes, RC and Lam, EWF and Hu, Y and Yague, E},
doi = {10.1007/s10549-017-4202-z},
journal = {Breast Cancer Research and Treatment},
pages = {461--474},
title = {Tumour suppressor EP300, a modulator of paclitaxel resistance and stemness, is down-regulated in metaplastic breast cancer},
url = {},
volume = {163},
year = {2017}

RIS format (EndNote, RefMan)

AB - PurposeWe have previously described a novel pathway controlling drug resistance, epithelial-to-mesenchymal transition (EMT) and stemness in breast cancer cells. Upstream in the pathway, three miRs (miR-106b, miR-93 and miR-25) target EP300, a transcriptional activator of E-cadherin. Upregulation of these miRs leads to the downregulation of EP300 and E-cadherin with initiation of an EMT. However, miRs regulate the expression of many genes, and the contribution to EMT by miR targets other than EP300 cannot be ruled out.MethodsWe used lentiviruses expressing EP300-targeting shRNA to downregulate its expression in MCF-7 cells as well as an EP300-knocked-out colon carcinoma cell line. An EP300-expression plasmid was used to upregulate its expression in basal-like CAL51 and MDA-MB-231 breast cancer cells. Drug resistance was determined by short-term proliferation and long-term colony formation assays. Stemness was determined by tumour sphere formation in both soft agar and liquid cultures as well as by the expression of CD44/CD24/ALDH markers. Gene expression microarray analysis was performed in MCF-7 cells lacking EP300. EP300 expression was analysed by immunohistochemistry in 17 samples of metaplastic breast cancer.ResultsCells lacking EP300 became more resistant to paclitaxel whereas EP300 overexpression increased their sensitivity to the drug. Expression of cancer stem cell markers, as well as tumour sphere formation, was also increased in EP300-depleted cells, and was diminished in EP300-overexpressing cells. The EP300-regulated gene signature highlighted genes associated with adhesion (CEACAM5), cytoskeletal remodelling (CAPN9), stemness (ABCG2), apoptosis (BCL2) and metastasis (TGFB2). Some genes in this signature were also validated in a previously generated EP300-depleted model of breast cancer using minimally transformed mammary epithelial cells. Importantly, two key genes in apoptosis and stemness, BCL2 and ABCG2, were also upregulated in EP300-knockout colon c
AU - Yague,E
AU - Asaduzzaman,M
AU - Constantinou,S
AU - Haoxiang,M
AU - Gallon,J
AU - Lin,ML
AU - Singh,P
AU - Raguz,S
AU - Ali,S
AU - Shousha,S
AU - Coombes,RC
AU - Lam,EWF
AU - Hu,Y
AU - Yague,E
DO - 10.1007/s10549-017-4202-z
EP - 474
PY - 2017///
SN - 1573-7217
SP - 461
TI - Tumour suppressor EP300, a modulator of paclitaxel resistance and stemness, is down-regulated in metaplastic breast cancer
T2 - Breast Cancer Research and Treatment
UR -
UR -
VL - 163
ER -